Zexi Zhang

Kaixuan Chen

Bruno Ameduri

Mao Chen

Fluoropolymer Nanoparticles Synthesized via Reversible-Deactivation Radical Polymerizations and Their Applications

Keywords: fluoropolymer, nanoparticle, polymer synthesis, reversible-deactivation radical polymerization

Fluorinated polymeric nanoparticles (FPNPs) combine unique properties of fluoropolymers and polymeric nanoparticles, stimulating massive interests in academia and industries for decades. However, fluoropolymers are not directly available from natural sources, resulting in developments of conventional techniques to obtain FPNPs based on free radical polymerizations. Recently, while increasing areas demand tailored FPNPs of complicated architectures and/or compositions as motivated by cutting-edge areas, such materials are difficult to be prepared through conventional approaches. During the past few years, reversible-deactivation radical polymerizations (RDRPs) have become powerful methods to afford well-defined polymers. Researchers have applied RDRPs to the fabrication of FPNPs, enabling the construction of particles with improved complexity in terms of structure, composition, morphology, functionality and so on. Such examples are classified into three categories. First, well-defined fluoropolymers synthesized via RDRPs have been utilized as precursors to form FPNPs. For example, self-folding, solution self-assembly have been developed for fluoropolymers of various sequences. Second, thermal-and photo-initiated RDRPs have been explored to realize in-situ preparations of FPNPs, facilitating the direct synthesis via polymerizationinduced self-assembly, cross-linking copolymerization to afford FPNPs of varied morphologies.

Third, grafting from inorganic nanoparticles has been investigated based on RDRPs. Importantly, these synthetic advancements have promoted investigations toward promising applications, including magnetic resonance imaging, biomedical delivery, energy storage, adsorption of perfluorinated alkyl substances, photosensitizers and so on. This review should present useful knowledge to researchers in polymer science and nanomaterials, and inspire innovative ideas for the synthesis of FPNPs and expand their applications.

INTRODUCTION

Polymeric nanoparticles (PNPs) play an important role in nanomaterials due to their interesting physical and chemical properties caused by high relative surface area, quantum size effects, as well as characteristics brought from polymers (e.g., mechanical strength, chemical structure, polarity, solubility). [START_REF] Ramos | Cationic Polymer Nanoparticles and Nanogels: From Synthesis to Biotechnological Applications[END_REF][START_REF] Wu | Chpater 7 -Polymer Nanoparticles[END_REF][START_REF] Adhikari | Polymer nanoparticles-preparations, applications and future insights: a concise review[END_REF][START_REF] Li | Polymer-encapsulated organic nanoparticles for fluorescence and photoacoustic imaging[END_REF][START_REF] Rao | Polymer nanoparticles: Preparation techniques and size-control parameters[END_REF][START_REF] Mavila | Intramolecular Cross-Linking Methodologies for the Synthesis of Polymer Nanoparticles[END_REF] Fluorinated polymeric nanoparticles (FPNPs) combine attributes of both PNPs and unique properties of fluoropolymers, such as outstanding chemical and temperature stability, high hydrophobicity, low surface energy, low refractive index and others, and have stimulated massive interests in both academia and industries. [START_REF] Ebnesajjad | Introduction to Fluoropolymers: Materials, Technology, and Applications[END_REF][START_REF] Scheirs | Modern Fluoropolymers: High Performance Polymers for Diverse Applications[END_REF][START_REF] Améduri | Applications[END_REF][START_REF] Améduri | Fascinating Fluoropolymers and Their Applications[END_REF] However, fluoropolymers are not available from natural sources. As a result, people have developed various synthetic approaches to obtain FPNPs, leading to fluorinated materials of many applications in coatings, paintings, additives, electronics, photonics, and so forth during past decades. [START_REF] Améduri | Applications[END_REF][START_REF] Smith | Handbook of Fluoropolymer Science and Technology[END_REF][START_REF] Hougham | Fluoropolymers: Synthesis and Applications[END_REF] Conventionally, the most important strategy for the synthesis of FPNPs relies on free radical polymerization mechanism, which is compatible with water and has been largely employed in industry. A variety of synthetic techniques, such as emulsion polymerization, mini-emulsion polymerization, micro-emulsion polymerization, polymerization in supercritical fluids, have been developed to afford FPNPs of different morphologies, sizes and compositions, as well as FPNPbased mixtures (e.g., emulsions) of desirable formulations, concentrations and other features through free radical processes. [START_REF] Hollamby | Fluorinated microemulsions as reaction media for fluorous nanoparticles[END_REF][START_REF] Lopez | Fluoropolymer Nanoparticles Prepared Using Trifluoropropene Telomer Based Fluorosurfactants[END_REF][START_REF] Li | Study on Emulsion Polymerization of Fluorinated Acrylate and its Application[END_REF][START_REF] Yamauchi | Fluoropolymer emulsions[END_REF][START_REF] Nenov | Fluorous miniemulsions: A powerful tool to control morphology in metallocene-catalyzed propene polymerization[END_REF][START_REF] Suwa | Emulsifier-free emulsion polymerization of tetrafluoroethylene by radiation. II. Effects of reaction conditions on polymer particle size and number[END_REF][START_REF] Xu | Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT[END_REF][START_REF] Kim | Emulsion polymerization of tetrafluoroethylene: effects of reaction conditions on particle formation[END_REF] Fluorinated monomers including semi-fluorinated (meth)acrylates, tetrafluoroethylene (TFE), chlorotrifluoroethylene (CTFE), vinylidene fluoride (VDF), trifluoroethylene (TrFE) have been successfully adopted to yield FPNPs in water and organic solvents. FPNPs of different types have also been engineered to broaden their application scope. [START_REF] Boschet | Co)polymers of chlorotrifluoroethylene: synthesis, properties, and applications[END_REF][START_REF] Puts | Polytetrafluoroethylene: Synthesis and Characterization of the Original Extreme Polymer[END_REF] For example, people have synthesized matrix particles, whose entire compositions are almost the same fluoropolymers, and core-shell particles that contain non-fluorinated and fluorinated polymers, simultaneously. [START_REF] Xu | Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT[END_REF][START_REF] Kim | Emulsion polymerization of tetrafluoroethylene: effects of reaction conditions on particle formation[END_REF][START_REF] Banerjee | A degradable fluorinated surfactant for emulsion polymerization of vinylidene fluoride[END_REF][START_REF] Landfester | Convenient Synthesis of Fluorinated Latexes and Core-Shell Structures by Miniemulsion Polymerization[END_REF][START_REF] Brandl | Poly(meth)acrylate-PVDF core-shell particles from emulsion polymerization: preferential formation of the PVDF β crystal phase[END_REF] However, free radical polymerizations lack control over chain growth, which frequently yield polymers of unpredictable chain lengths, broad dispersities, and are difficult to approach polymer sequences, topologies of increased complexity.

In recent years, while more and more investigations have disclosed the importance of preparing well-defined polymers to achieve interesting properties, and revealed the necessities of macromolecular engineering in cutting-edge areas, [START_REF] Lv | Fluoropolymers in biomedical applications: state-of-the-art and future perspectives[END_REF][START_REF] Corrigan | Reversibledeactivation radical polymerization (Controlled/living radical polymerization): From discovery to materials design and applications[END_REF][START_REF] Mohammad | Macromolecular engineering approach for the preparation of new architectures from fluorinated olefins and their applications[END_REF][START_REF] Lopez | Designing polymers for advanced battery chemistries[END_REF] it is desirable to develop novel synthetic pathways to tailor FPNPs and explore properties of those customized materials.

During the past two decades, reversible-deactivation radical polymerizations (RDRPs) have become powerful methods to afford polymers of predefined molar masses, low dispersities and well-defined structures. [START_REF] Corrigan | Reversibledeactivation radical polymerization (Controlled/living radical polymerization): From discovery to materials design and applications[END_REF][START_REF] Braunecker | Controlled/living radical polymerization: Features, developments, and perspectives[END_REF][START_REF] Jenkins | Terminology for reversible-deactivation radical polymerization previously called "controlled" radical or "living" radical polymerization (IUPAC Recommendations[END_REF][START_REF] Truong | A comparison of RAFT and ATRP methods for controlled radical polymerization[END_REF][START_REF] Parkatzidis | Recent Developments and Future Challenges in Controlled Radical Polymerization: A 2020 Update[END_REF] For example, atom transfer radical polymerization (ATRP), [START_REF] Matyjaszewski | Atom Transfer Radical Polymerization[END_REF][START_REF] Matyjaszewski | Macromolecular engineering by atom transfer radical polymerization[END_REF] reversible addition-fragmentation chain transfer (RAFT) polymerization, [START_REF] Moad | Toward Living Radical Polymerization[END_REF][START_REF] Chiefari | Living Free-Radical Polymerization by Reversible Addition-Fragmentation Chain Transfer: The RAFT Process[END_REF][START_REF] Perrier | Macromolecular design via reversible addition-fragmentation chain transfer (RAFT)/xanthates (MADIX) polymerization[END_REF] nitroxide-mediated polymerization (NMP), [START_REF] Hawker | New Polymer Synthesis by Nitroxide Mediated Living Radical Polymerizations[END_REF] iodine transfer polymerization (ITP) [START_REF] Oka | Vinylidene Fluoride-Hexafluoropropylene Copolymer having Terminal Iodines[END_REF][START_REF] David | Use of Iodocompounds in Radical Polymerization[END_REF] have been systematically developed, and widely employed for controlled polymer synthesis. With those methods, polymer sequences (e.g., block, random, alternating), topologies (e.g., (hyper)branch, brush) could be finely tuned via rational design of (macro)initiators, chain transfer agents (CTAs), catalysts, reaction strategies (e.g., graft polymerization, gradual addition of agent), and/or combination with suitable monomers.

Motivated by the synthetic advantages, RDRPs have been applied to the synthesis of fluoropolymers, [START_REF] Mohammad | Macromolecular engineering approach for the preparation of new architectures from fluorinated olefins and their applications[END_REF] which enable the construction of FPNPs with improved complexity in terms of chemical composition, morphology, functionality and so on. The synthetic methods could be mainly classified into two categories (Scheme 1). First, well-defined polymers synthesized via RDRPs have been utilized as precursors to yield FPNPs (section 2). In this category, the solution selfassembly of diblock, multi-block copolymers with fluorinated segments provides an important pathway to create FPNPs with attractive architectures, properties and functions. Beyond the aggregation of many macromolecular chains, it has been reported that the self-folding strategy of single fluorinated chains of block, even random sequences, could be highly reversible under folding/unfolding conditions. Second, FPNPs are directly generated during the process of RDRPs under thermal or light-irradiation reaction conditions (section 3). Macroinitiators of controlled chain length, customized side groups are adopted for chain-extensions via RDRPs, leading to polymerization-induced self-assembly (PISA) that enables the in-situ formation of a series of morphologies such as spheres, worms, cylinders, vesicles and others at variable mass fractions.

To enhance the stability of particles, transformations with small molecular cross-linkers are also examined to generate covalently cross-linked polymeric networks mediated by RDRPs. Additionally, with inorganic nanoparticles as substrates, surface-initiated RDRPs (SI-RDRPs) have been developed with fluorinated monomers to yield nanoparticles with fluoropolymer coatings (section 4). Based on the synthetic advancements, FPNPs have been investigated for a variety of potential applications (section 5) including magnetic resonance imaging (MRI), delivery of drugs, genes and proteins, energy materials, adsorption of perfluoroalkyl substances (PFASs), photodynamic therapy (PDT) and so on. Scheme 1. Schematic illustration for the preparation of FPNPs based on RDRPs and applications in diverse directions. Reproduced with permission from ref [START_REF] Quan | Fluorous-Core Nanoparticle-Embedded Hydrogel Synthesized via Tandem Photo-Controlled Radical Polymerization: Facilitating the Separation of Perfluorinated Alkyl Substances from Water[END_REF] . Copyright 2020 American Chemical Society. Reproduced with permission from ref [START_REF] Liu | Sensitization of Hypoxic Tumor to Photodynamic Therapy via Oxygen Self-Supply of Fluorinated Photosensitizers[END_REF] . Copyright 2019 American Chemical Society.

Up to now, a number of reviews have summarized synthetic methods, techniques, as well as applications of PNPs, [START_REF] Ramos | Cationic Polymer Nanoparticles and Nanogels: From Synthesis to Biotechnological Applications[END_REF][START_REF] Wu | Chpater 7 -Polymer Nanoparticles[END_REF][START_REF] Adhikari | Polymer nanoparticles-preparations, applications and future insights: a concise review[END_REF][START_REF] Li | Polymer-encapsulated organic nanoparticles for fluorescence and photoacoustic imaging[END_REF][START_REF] Rao | Polymer nanoparticles: Preparation techniques and size-control parameters[END_REF][START_REF] Mavila | Intramolecular Cross-Linking Methodologies for the Synthesis of Polymer Nanoparticles[END_REF] and discussed the synthesis, properties of main-chain and side-chain fluoropolymers. [START_REF] Boschet | Co)polymers of chlorotrifluoroethylene: synthesis, properties, and applications[END_REF][START_REF] Puts | Polytetrafluoroethylene: Synthesis and Characterization of the Original Extreme Polymer[END_REF][START_REF] Lv | Fluoropolymers in biomedical applications: state-of-the-art and future perspectives[END_REF][START_REF] Mohammad | Macromolecular engineering approach for the preparation of new architectures from fluorinated olefins and their applications[END_REF] Researchers have also systematically summarized methods and mechanisms of RDRPs. [START_REF] Corrigan | Reversibledeactivation radical polymerization (Controlled/living radical polymerization): From discovery to materials design and applications[END_REF][START_REF] Braunecker | Controlled/living radical polymerization: Features, developments, and perspectives[END_REF][START_REF] Jenkins | Terminology for reversible-deactivation radical polymerization previously called "controlled" radical or "living" radical polymerization (IUPAC Recommendations[END_REF][START_REF] Truong | A comparison of RAFT and ATRP methods for controlled radical polymerization[END_REF][START_REF] Parkatzidis | Recent Developments and Future Challenges in Controlled Radical Polymerization: A 2020 Update[END_REF] In recent years, increasing examples have disclosed attractive features of well-defined nanoparticles and fluoropolymers for high-tech purposes. This present review aims at highlighting advances of RDRPs employed to fabricate FPNPs, and the application studies of those customized FPNPs.

PREPARATION OF NANOPARTICLES WITH FLUOROPOLYMERS PREFORMED VIA RDRPS

Self-Assembly of Multiple Fluoropolymer Chains

Self-assembly has been developed as a powerful strategy for the fabrication of particles with ordered patterns. [START_REF] Xu | Self-assembly of Amphiphilic Alternating Copolymers[END_REF][START_REF] Derry | Polymerization-induced self-assembly of block copolymer nanoparticles via RAFT non-aqueous dispersion polymerization[END_REF] Organic and inorganic compounds, polymers could be utilized as sub-units for self-assembly. Amphiphilic block copolymers can associate into nanostructures as driven by the dynamic interfacial equilibrium between solvated and solvophobic segments. [START_REF] Hayward | Tailored Assemblies of Block Copolymers in Solution: It Is All about the Process[END_REF] Traditionally, the preparation of self-assembled PNPs generally includes three steps: 1) synthesis and purification of block copolymers; 2) dissolving copolymers in suitable solvents; 3) microphase separation in a diluted solution as driven by solvophobicity of one of the blocks in copolymers. [START_REF] D'agosto | RAFT-Mediated Polymerization-Induced Self-Assembly[END_REF] However, this strategy often provides PNPs of low concentrations (<1% w/w) in solvents. Benefited from RDRPs and other controlled/living polymerizations, tailor-designed block copolymers of predetermined block sequences, functional groups, block ratios, or hierarchical topologies (e.g., block on hyperbranched) could be prepared with easily accessible starting materials, furnishing great opportunities to establish a variety of morphologies. [START_REF] Hirao | Precise synthesis and surface structures of architectural per-and semifluorinated polymers with well-defined structures[END_REF] Due to the fluorophobic effect, [START_REF] Marsh | Tunable Fluorophobic Effect Determines Nanoparticle Dispersion in Homopolymers and Block Polymers[END_REF][START_REF] Percec | Fluorophobic Effect Induces the Self-Assembly of Semifluorinated Tapered Monodendrons Containing Crown Ethers into Supramolecular Columnar Dendrimers Which Exhibit a Homeotropic Hexagonal Columnar Liquid Crystalline Phase[END_REF] highly crystalline fluoropolymers are normally neither miscible with water nor with most organic solvents. Consequently, copolymers with fluorinated segments have a strong tendency toward self-assembly when dispersed in solvents, and exhibit low critical concentrations. The unique fluorophobic property has enabled the preparation of FPNPs with both fluorophilic, lipophilic and hydrophilic segments, [START_REF] Lodge | Simultaneous, Segregated Storage of Two Agents in a Multicompartment Micelle[END_REF][START_REF] Li | Multicompartment Micelles from ABC Miktoarm Stars in Water[END_REF] which expands the potentials of nanomaterials. However, poly(VDF) and copolymers of VDF are soluble in polar solvents, [START_REF] Marshall | On the Solubility and Stability of Polyvinylidene Fluoride[END_REF] limiting the preparation of nanoparticles in related solvents. Next, we will discuss the preparation of FPNPs by using fluoropolymers prepared with different RDRPs as bellows.

Fluoropolymers Synthesized via ATRP

The advancements of ATRP have allowed the construction of complex polymers using readily available activated alkyl halides as initiators and metal complexes as catalysts under thermal conditions. [START_REF] Matyjaszewski | Atom Transfer Radical Polymerization[END_REF] The copper-catalyzed activation/deactivation equilibrium facilitates achieving good structural fidelity via simple reliable systems. As influenced by the monomer scope, fluorinated (meth)acrylates and styrene (St) derivates are most commonly employed to afford FPNPs based on ATRP. [START_REF] Gong | Controlled/Living Radical Polymerization of Semifluorinated (Meth)acrylates[END_REF][START_REF] Yao | Fluorinated poly(meth)acrylate: Synthesis and properties[END_REF] For example, DeSimone, [START_REF] Betts | New materials by controlled radical polymerization: controlled radical polymerization methods for the synthesis of nonionic surfactants for CO2[END_REF] Matyjaszewski, [START_REF] Xia | Atom Transfer Radical Polymerization in Supercritical Carbon Dioxide[END_REF] Boutevin, [START_REF] Otazaghine | Controlled radical polymerization of nbutyl α-Fluoroacrylate. 1. Use of atom transfer radical polymerization as the polymerization method[END_REF] Haddleton [START_REF] Perrier | Preparation of Fluorinated Copolymers by Copper-Mediated Living Radical Polymerization[END_REF] and co-workers demonstrated the controlled synthesis of fluorinated poly(meth)acrylates with alkyl bromides and copper catalysts since the seminal works of ATRP. [START_REF] Matyjaszewski | Controlled/"living" radical polymerization. atom transfer radical polymerization in the presence of transition-metal complexes[END_REF] In 2001, the Wooley's group [START_REF] Becker | Diblock copolymers, micelles, and shellcrosslinked nanoparticles containing poly(4-fluorostyrene): Tools for detailed analyses of nanostructured materials[END_REF] reported the synthesis of poly(4-fluorostyrene)-b-poly(methyl acrylate) (poly(FSt)-b-poly(MA)) via a two-step Cu-catalyzed ATRP initiated from (1bromoethyl)benzene using a pentamethyldiethylenetriamine ligand (Figure 1). After hydrolysis of the poly(methyl acrylate) (poly(MA)) segment into poly(acrylic acid) (poly(AA)), micelles were formed with the obtained amphiphilic diblock copolymers in aqueous mixtures, which were further stabilized by intra-micellar covalent cross-linking of poly(AA) blocks to generate shell-crosslinked FPNPs. The nanostructures of obtained samples were visualized by both atomic force microscopy (AFM) and transmission electron microscopy (TEM), providing multimodal size distributions, as well as clusters of both small and large shell-crosslinked FPNPs.

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Submitted to Chemical Reviews Besides diblock copolymers, amphiphilic ABA triblock copolymers were prepared based on Cu-catalyzed chain-extension polymerization from telechelic poly(ethylene oxide) (PEO) macroinitiator with two alkyl bromide terminals to afford FPNPs. [START_REF] Hussain | Poly(ethylene oxide)-and Poly(perfluorohexylethyl methacrylate)-Containing Amphiphilic Block Copolymers: Association Properties in Aqueous Solution[END_REF] Huang and co-workers [START_REF] Xu | Perfluorocyclobutyl Aryl Ether-Based ABC Amphiphilic Triblock Copolymer[END_REF] demonstrated the synthesis of amphiphilic ABC triblock copolymers composed of hydrophilic PEO and poly(methacrylic acid) (poly(MAA)) segments, and hydrophobic poly(p- (2-(4-biphenyl) perfluorocyclobutoxy)phenyl methacrylate) sequence via Cu-catalyzed two-step chain-extensions from a PEO-based macroinitiator, which provided nanoscale micelles that can encapsulate hydrophilic (e.g., rhodamine) and hydrophobic (e.g., pyrene) molecules in neutral aqueous solution.

Tsapis and co-workers [START_REF] Houvenagel | Comb-Like Fluorophilic-Lipophilic-Hydrophilic Polymers for Nanocapsules as Ultrasound Contrast Agents[END_REF] reported the synthesis of ABC triblock copolymers composed of PEO, polylactide and poly(heptadecafluorodecyl methacrylate) (poly(17FDMA)) segments based on the combination of ring-opening polymerization and ATRP starting from PEO macroinitiator. The amphiphilic triblock copolymers formed nanocapsules (mean hydrodynamic diameter (Dh) ≈ 110-140 nm) via an emulsion evaporation process, allowing the encapsulation of ultrasound contrast agents (UCAs) of perfluorooctyl bromide.

Howdle et al. [START_REF] Woods | Dispersion Polymerization of Methyl Methacrylate in Supercritical Carbon Dioxide: An Investigation into Stabilizer Anchor Group[END_REF] employed perfluoropolyether (PFPE) as the CO2-philic portion, and prepared PFPE-b-poly(methyl methacrylate) (PFPE-b-poly(MMA)) diblock copolymers via ATRP in supercritical carbon dioxide (scCO2). Because fluoropolymers possess good solubility in scCO2, the fluorinated macroinitiator showed a dramatic impact on the dispersion polymerization of MMA, affording excellent yields (up to 97%) of spherical particles with mean particle diameter (Dn) down to 1.4 μm. [START_REF] Discekici | Light-Mediated Atom Transfer Radical Polymerization of Semi-Fluorinated (Meth)acrylates: Facile Access to Functional Materials[END_REF] Although this method provided highly uniform sizes, fluorinated particles of smaller sizes could not be achieved. Later, Dong and co-workers [START_REF] Yang | Synthesis of fluorinated diblock copolymer by ATRP and its application of PAVAc polymerization in ScCO2[END_REF] via the photo-mediated ATRP. The copolymer was hydrolyzed to poly(AA)-b-poly(TFEA) that forms micelles of Dh ≈ 30 nm and a zeta potential of -26 mV in aqueous solution (Scheme 3).

Fluoropolymers Synthesized via RAFT Polymerization

RAFT polymerizations employ sulfur-based compounds (e.g., trithiocarbonates, dithioesters, dithiocarbamates, xanthates) as CTAs (or RAFT agents) in the presence of radical initiators (azobisisobutyronitrile = AIBN, peroxides), and have been normally conducted under thermal conditions. [START_REF] Moad | Toward Living Radical Polymerization[END_REF][START_REF] Hill | Expanding the Scope of RAFT Polymerization: Recent Advances and New Horizons[END_REF][START_REF] Perrier | 50th Anniversary Perspective: RAFT Polymerization-A User Guide[END_REF] While radicals yielded from initiators could react with CTAs and generate carboncentered radical intermediates stabilized by sulfur atoms, such intermediates undergo carbonsulfur bond cleavage to give propagating radicals. The propagating chains could perform degenerative chain transfer with other CTAs to implement dynamic chain-growth control. [START_REF] Keddie | RAFT Agent Design and Synthesis[END_REF] A number of groups, such as the Lacroix-Desmazes, [START_REF] Ma | Synthesis of hydrophilic/CO2-philic poly(ethylene oxide)-bpoly(1,1,2,2-tetrahydroperfluorodecyl acrylate) block copolymers via controlled/living radical polymerizations and their properties in liquid and supercritical CO2[END_REF] Théato, [START_REF] Eberhardt | RAFT Polymerization of Pentafluorophenyl Methacrylate: Preparation of Reactive Linear Diblock Copolymers[END_REF] Ishihara, [START_REF] Inoue | Synthesis of sequence-controlled copolymers from extremely polar and apolar monomers by living radical polymerization and their phase-separated structures[END_REF] Terashima 78 groups, have disclosed the use of RAFT polymerization in preparing fluoropolymers. Although the vast majority of examples are focused on fluorinated (meth)acrylates and styrene derivatives, recent developments have revealed that RAFT agents are able to facilitate the controlled synthesis of main-chain fluoropolymers with gaseous fluoroalkenes. [START_REF] Guerre | An amphiphilic poly(vinylidene fluoride)-b-poly(vinyl alcohol) block copolymer: synthesis and self-assembly in water[END_REF][START_REF] Zhou | Main-Chain Fluoropolymers with Alternating Sequence Control via Light-Driven Reversible-Deactivation Copolymerization in Batch and Flow[END_REF][START_REF] Zhao | Controlled radical copolymerization of fluoroalkenes by using light-driven redox-relay catalysis[END_REF][START_REF] Jiang | Photoorganocatalyzed Reversible-Deactivation Alternating Copolymerization of Chlorotrifluoroethylene and Vinyl Ethers under Ambient Conditions: Facile Access to Main-Chain Fluorinated Copolymers[END_REF][START_REF] Quan | Visible-Light-Enabled Organocatalyzed Controlled Alternating Terpolymerization of Perfluorinated Vinyl Ethers[END_REF][START_REF] Quan | Organocatalyzed Controlled Copolymerization of Perfluorinated Vinyl Ethers and Unconjugated Monomers Driven by Light[END_REF][START_REF] Girard | Direct Synthesis of Vinylidene Fluoride-Based Amphiphilic Diblock Copolymers by RAFT/MADIX Polymerization[END_REF][START_REF] Bouad | RAFT polymerisation of trifluoroethylene: the importance of understanding reverse additions[END_REF] In 2006, Jerome and co-workers [START_REF] Grignard | Controlled synthesis of carboxylic acid end-capped poly(heptadecafluorodecyl acrylate) and copolymers with 2-hydroxyethyl acrylate[END_REF] prepared diblock copolymers of heptadecafluorodecyl acrylate (17FDA) and 2-hydroxyethyl acrylate (HEA) using a trithiocarbonate compound via a twostep RAFT polymerization. As measured by TEM, the amphiphilic copolymers formed spherical

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Submitted to Chemical Reviews micelles with an average diameter of 50 to 100 nm. Increasing the concentration for 2-hydroxyethyl acrylate caused the precipitation of poly(17FDA) macroinitiator, resulting in copolymers of limited molar masses.

In 2010, He and co-workers 88 applied two-step RAFT polymerizations to yield diblock copolymers of hexafluorobutyl methacrylate (6FBMA) and poly(propylene glycol) acrylate (PPGA) as monomers with dithiobenzoate agent. Although the poly(PPGA) block merely provides moderate hydrophilic property, the poly(6FBMA)-b-poly(PPGA) copolymer self-assembled in aqueous solution, resulting in the accumulation of 40-50 micelles into one aggregate (diameter ≈ 50-60 nm), where micelles were loosely packed as observed by TEM. The Singha group [START_REF] Koiry | Fluorinated amphiphilic block copolymers via RAFT polymerization and their application as surf-RAFT agent in miniemulsion polymerization[END_REF] prepared diblock copolymers with PEGMA and heptafluorobutyl acrylate (7FBA) as repeating units. The copolymers formed spherical micelles consisting of fluorinated blocks as cores and hydrophilic blocks as flexible coronas with an average diameter of about 140 nm as measured by TEM. When MMA was used instead of PEGMA, morphologies of block copolymers changed from lamellar to spherical micelles as influenced by the volume ratio of tetrahydrofuran/methyl ethyl ketone solvents. [START_REF] Koiry | Syntheses and morphologies of fluorinated diblock copolymer prepared via RAFT polymerization[END_REF] Diblock copolymers were also prepared with poly(methacrylic acid) (poly(MAA)) as the first block and poly(TFEMA)-co-poly(hexafluorobutyl acrylate) (poly(TFEMA)-co-poly(6FBA)) as the second block via RAFT emulsion polymerization under aqueous conditions, providing core-shell FPNPs with Dh ≈ 56-93 nm by DLS measurement. [START_REF] Jiang | Hydrophobic films of acrylic emulsion by incorporation of fluorine-based copolymer prepared through the RAFT emulsion copolymerization[END_REF] Authors proposed that the incorporation of less fluorinated TFEMA to copolymerize with 6FBA could improve the overall conversion of fluorinated monomers. 3). Notably, authors revealed that sequences of the triblock copolymers have a clear impact on micelle morphologies. For instance, the hydrophilic-lipophilic-fluorophilic sequence formed multicompartment morphology with core-shell-corona ultrastructure (Figure 3a), the lipophilic-hydrophilic-fluorophilic sequence yielded "patched double micelle" ultrastructure (Figure 3b). Later, the same team 93 used the same synthetic strategy for the preparation of triblock copolymers of PEO-based acrylate, benzyl acrylate and 7FBA, affording diverse structures as visualized by cryo-TEM, such as core-shell-corona ultrastructures, spherical and bispherical micelles, "soccer ball" morphologies and others. The coexistence of both hydrocarbon and fluorocarbon domains side by side might provide opportunities for the selective/independent adsorb and release of different chemicals, mimicking biologically related delivery of various substances.

Instead of successive RDRPs of three different monomers, Huang et al. [START_REF] Liu | Construction of well-defined difluoromethylthiocontaining amphiphilic homopolymers by RAFT polymerization[END_REF] modifications to obtain porphyrin-functionalized FPNPs. [START_REF] Que | Enhancing Photodynamic Therapy Efficacy by Using Fluorinated Nanoplatform[END_REF] In 2014, Zentel and co-workers [START_REF] Nuhn | Sizedependent knockdown potential of siRNA-loaded cationic nanohydrogel particles[END_REF] reported the synthesis of diblock copolymers via two-step RAFT polymerizations of (pentafluorophenyl methacrylate (PFPMA)) and tri(ethylene glycol)methyl ether methacrylate. With self-assembled aggregates formed by copolymers of different chain lengths, nanogel particles of different diameters (40 and 100 nm) were yielded after adding spermine as a cross-linking agent. Those nanohydrogel materials were further employed to investigate gene knockdown ability.

In 2016, the Huang's group [START_REF] Que | Enhancing Photodynamic Therapy Efficacy by Using Fluorinated Nanoplatform[END_REF] Thanks to the thermo-responsive property of poly(DFEA) and redox-responsive property of poly(FcCEA), authors investigated the "smart" FPNPs for [START_REF] Xu | Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT[END_REF] F MRI therapy and diagnostic purposes (section 5.1).

Beyond side-chain fluorinated polymers, the synthesis of main-chain fluoropolymers via RAFT polymerization has also been probed to provide FPNPs. In 2017, Ladmiral and co-workers [START_REF] Guerre | An amphiphilic poly(vinylidene fluoride)-b-poly(vinyl alcohol) block copolymer: synthesis and self-assembly in water[END_REF] reported the first synthesis of amphiphilic diblock copolymers of poly(VDF)-b-poly(vinyl acetate) (poly(VDF)-b-poly(VAc)) through sequential RAFT polymerizations of VDF and VAc (Figure 4) using in water. [START_REF] Guerre | An amphiphilic poly(vinylidene fluoride)-b-poly(vinyl alcohol) block copolymer: synthesis and self-assembly in water[END_REF] Reproduced with permission from ref [START_REF] Guerre | An amphiphilic poly(vinylidene fluoride)-b-poly(vinyl alcohol) block copolymer: synthesis and self-assembly in water[END_REF] . Copyright 2017 Royal Society of Chemistry.

In 2021, D'Agosto, Lansalot et al. [START_REF] Fuentes-Exposito | Surfactant-free emulsion polymerization of vinylidene fluoride mediated by RAFT/MADIX reactive poly(ethylene glycol) polymer chains[END_REF] disclosed the surfactant-free synthesis of poly(VDF) latexes via RAFT polymerization with xanthate-functionalized PEG as a macro-CTA and potassium persulfate as an initiator (Figure 5). These authors proposed degradative chain transfer onto PEG backbone, providing PEG radicals, followed by coupling reaction with radicals of oligo(VDF). 100 The employment of a very low macro-CTA amount (0.8 wt%) clearly reduced sizes of FPNPs (e.g., 72

nm), in comparison to polymerization using PEG-OH (234 nm). The reliability of this method was evidenced by scale-up polymerization in a 4 L vessel. Recently, inspired by the combinations of photoredox catalysis and RAFT polymerization, 104- 108 Chen and co-workers demonstrated the controlled polymerizations of a variety of fluorinated monomers including semi-fluorinated (meth)acrylates, 109, 110 CTFE [START_REF] Zhou | Main-Chain Fluoropolymers with Alternating Sequence Control via Light-Driven Reversible-Deactivation Copolymerization in Batch and Flow[END_REF][START_REF] Jiang | Photoorganocatalyzed Reversible-Deactivation Alternating Copolymerization of Chlorotrifluoroethylene and Vinyl Ethers under Ambient Conditions: Facile Access to Main-Chain Fluorinated Copolymers[END_REF] and perfluorinated vinyl ethers (PFVEs) [START_REF] Quan | Visible-Light-Enabled Organocatalyzed Controlled Alternating Terpolymerization of Perfluorinated Vinyl Ethers[END_REF][START_REF] Quan | Organocatalyzed Controlled Copolymerization of Perfluorinated Vinyl Ethers and Unconjugated Monomers Driven by Light[END_REF] with or without comonomers under ambient pressure and at room temperature without using any metal catalyst. Besides homo-polymerization of semi-fluorinated (meth)acrylates, emulsions were observed during the copolymerization, 109,110 alternating copolymerization, alternating terpolymerization of fluoroalkenes (e.g., CTFE, PFVEs). [START_REF] Zhou | Main-Chain Fluoropolymers with Alternating Sequence Control via Light-Driven Reversible-Deactivation Copolymerization in Batch and Flow[END_REF][START_REF] Jiang | Photoorganocatalyzed Reversible-Deactivation Alternating Copolymerization of Chlorotrifluoroethylene and Vinyl Ethers under Ambient Conditions: Facile Access to Main-Chain Fluorinated Copolymers[END_REF][START_REF] Quan | Visible-Light-Enabled Organocatalyzed Controlled Alternating Terpolymerization of Perfluorinated Vinyl Ethers[END_REF] Although systematic studies regarding the preparation of FPNPs based on such photoredox-mediated RDRP methods have yet to come, the controlled accesses toward main-chain fluoropolymers supply alternative paths to multi-geometry PNPs that could be achieved by complex sequences. 111-113

Fluoropolymers Synthesized via ITP

ITP is a degenerative chain transfer (DT) polymerization with organic iodocompounds as CTAs. [START_REF] David | Use of Iodocompounds in Radical Polymerization[END_REF] The initiating radicals are generated by the thermal decomposition of conventional initiators.

The exchange of iodine from CTA (iodine compound) to the propagating radical results in the formation of a dormant polymer chain. Due to the reversible transfer step, the significantly lowered concentration of free radicals contributes to minimizing undesirable side reactions (irreversible chain terminations), which is essential to promote chain-growth control during monomer consumption. [START_REF] Mohammad | Macromolecular engineering approach for the preparation of new architectures from fluorinated olefins and their applications[END_REF]114 VDF is one of the most attractive fluoroalkenes utilized to prepare main-chain fluoropolymers, 115,116 which are widely explored for applications as coatings, membranes, polymer electrolytes and many more. 117,118 ITP has been demonstrated as an effective means to furnish customized main-chain fluorinated copolymers of VDF and other fluorinated/non-fluorinated comonomers of block or random sequences. 114,[119][120][121][122][123] Although ITP is considered as the oldest technique (pioneered in 1979) and a facile approach to generating fluoropolymers, the relatively slow chain transfer increases difficulties in obtaining very narrow molar mass distribution and high chain-end structural fidelity. 115 When many mainchain fluorinated copolymers are formed with CH2-I, such chain-end groups are not readily reactive for reversible deactivation, which often cause the accumulation of less reactive chains and pose challenges for chain-extension reactions. 124,125 In addition, polymerizations of gaseous fluoroalkenes require high-pressure metallic vessels and elevated temperatures, which are problematic with conventional reaction techniques and are difficult to be handled by most laboratories. Consequently, when VDF and other gaseous fluoroalkenes are desirable to prepare FPNPs, free-radical emulsion polymerizations are remaining in widespread use, where emulsion ITPs are explored for targets with block sequence or functional composition. 123 A few investigations proposing to provide information about the controlled polymerization behaviors are usually reported as patents, [START_REF] Oka | Vinylidene Fluoride-Hexafluoropropylene Copolymer having Terminal Iodines[END_REF]126 which lack detailed descriptions of the chemical structure, molar masses, polymer dispersity, chain-end fidelity and reaction kinetics.

In 2009, Ameduri and co-workers 116 reported the iodine transfer copolymerization of VDF with α-trifluoromethacrylic acid (TFMA) in an aqueous medium in the presence of 1-perfluorohexyl iodide (nC6F13I) or 1,4-diodoperfluorobutane (IC4F8I) as CTAs, which realized a surfactant-free "emulsion" copolymerization without any surfactant (Scheme 8). As characterized by 1 H and [START_REF] Xu | Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT[END_REF] F nuclear magnetic resonance (NMR), the controllability of the VDF copolymerization was improved by adding a small amount of TFMA. Meanwhile, the presence of TFMA enabled the formation of a stable emulsion and reduction of the particle size by one order of magnitude to smaller than 200 nm as analyzed by light scattering. Scheme 8. Iodine transfer copolymerization of VDF and α-trifluoromethacrylic acid. 116 In 2020, Cheng and co-workers 127 demonstrated the development of photo-controlled iodinemediated RDRP to obtain main-chain fluorinated alternating copolymers (Scheme 9). In this method, α,ω-diiodoperfluoroalkane and α,ω-nonconjugated diene were utilized as comonomers using Ru-based photocatalyst. Authors proposed that a dynamic equilibrium between the propagating and dormant species was facilitated by the oxygen-iodine interaction in acetone. With the alternating copolymer as a macroinitiator, authors prepared the block copolymer with ACS Paragon Plus Environment Submitted to Chemical Reviews poly(PEGMA) as a second block. When this unprecedented block copolymer was dispersed in a pre-mixed solvent of tetrahydrofuran/H2O, it generated FPNPs of an average diameter of 147 nm as determined by DLS measurement. Scheme 9. Synthesis of alternating fluoropolymers via photopolymerization and post modification. 127

Fluoropolymers Synthesized via NMP

NMP represents another important category of RDRPs, where alkoxyamine compounds have been employed as initiators under thermal conditions. [START_REF] Hawker | New Polymer Synthesis by Nitroxide Mediated Living Radical Polymerizations[END_REF] An alkoxyamine undergoes carbon-oxygen bond cleavage, and generates carbon-centered radial and a nitroxide radical. While the carboncentered radical initiates propagation, the nitroxide radical acts as a persistent radical, which could reversibly terminate propagating species. 128 For example, poly(pentafluorostyrene) (poly(PFSt)) chains were grafted onto the surface of silica nanoparticles. 130

Self-Folding of Single Fluoropolymer Chains

Biomacromolecules in nature always provide inspiration to polymer scientists. The precise arrangement of functional groups and the well-defined three-dimensional architectures of folded single chains enable unique properties and functions for biomacromolecules (e.g., proteins, nucleic acids, enzymes) of both surfaces and interiors. 131 Self-folding of single synthetic polymer chains provides possibilities to obtain small PNPs with tailored functions in the sub 20 nm dimension. 132 Massive efforts have been made to realize intramolecular linking of single polymer chains since 1962. 133 This strategy creates a promising pathway to engineering artificial and smart single-chain polymers that could be attractive for applications of nanoreactors, catalysis, gene/drug delivery, sensors, etc. 131,134 However, the synthesis of well-defined functional polymers of uniform molar masses and precisely ordered sequence still lies far behind many biomacromolecules.

RDRPs have shown outstanding compatibility with functional groups, and are reliable to tailor sequences and molar masses of polymers. Such synthetic methods have been frequently employed to preform customized polymers for self-folding purposes. 131,134 The intrachain selffolding has been achieved through covalent bonding, dynamic covalent bonding, and non-covalent interaction. 131,134 For the non-covalent bonding studies, interactions such as hydrogen bonding, host-guest interaction, hydrophobic interaction, coordination have been probed to generate folded single-chain polymeric nano-objects. 131,134 The unique properties of fluorine atom (strong electronegativity, fluorophobic effect [START_REF] Marsh | Tunable Fluorophobic Effect Determines Nanoparticle Dispersion in Homopolymers and Block Polymers[END_REF][START_REF] Percec | Fluorophobic Effect Induces the Self-Assembly of Semifluorinated Tapered Monodendrons Containing Crown Ethers into Supramolecular Columnar Dendrimers Which Exhibit a Homeotropic Hexagonal Columnar Liquid Crystalline Phase[END_REF] ) expanded possibilities of realizing highly reversible single-chain folding via non-covalent interaction in water and organic solvents. Later, the same group 137 employed a urea-bearing methacrylate substituted by two trifluoromethyl groups instead of 13FOMA with PEGMA (Figure 7). Electron-withdrawing property of trifluoromethyls decreases pKa of urea units and enhances hydrogen bonds for self-folding.

Notably, authors disclosed sequences have a clear impact on the self-folding or assembly for copolymers made of the same repeating units. For instance, copolymers of random sequences form spherical unimer micelles (Dh ≈ 16 nm). Meanwhile, copolymers of gradient (aggregates with Dh ≈ 104 nm, 87% unimer with Dh ≈ 13 nm) and block (aggregates with Dh ≈ 250 nm) sequences tend to provide different extents of aggregation of multiple chains as analyzed by DLS.

Galli, Mennucci and co-workers 138 synthesized random copolymers based on PEGMA and perfluorooctyl acrylate (13FOA) via ATRP. The copolymers afford single-chain nano-assemblies of Dh ≈ 4 nm, which can reversibly undergo multi-chain aggregation to larger nano-objects of Dh ≈ 390 nm above LCST of PEGMA segment. Beyond synthetic experiments, the authors conducted molecular dynamics simulations to disclose the formation of self-folded single polymer chains. As exemplified in Figure 8, the single-chain self-folding predicts prolate globular structure in water, where hydrophobic units are buried in the core of the nanostructure. In comparison, a much more open confirmation is given for the same macromolecule in chloroform.

IN SITU SYNTHESIS OF FPNPS VIA RDRPS

Different from solution self-assembly and self-folding, which are post-polymerization techniques that demand multiple steps and provide highly diluted PNPs in solvents, one-step synthesis of PNPs based on RDRP techniques have also been developed. Polymerization induced self-assemble (PISA) and covalent cross-linking based on RDRPs have allowed the direct preparation of FPNPs. Due to solubility issue of fluorinated monomers, such synthetic operations have been conducted in organic solvents via surfactant-free emulsion polymerization, or in water using hydrophilic macro-CTAs/initiators as stabilizers via emulsion polymerization.

PISA Mediated by RDRPs

PISA allows in situ preparation of self-assembled PNPs via chain-extensions from preformed solvophilic polymers (e.g., macro-CTAs, macroinitiators), where solvophobic blocks have been generated under dispersion or emulsion polymerizations as mediated by RDRPs. [139][140][141] In contrast to traditional self-assembly and self-folding operations, PISA transformations have been achieved under relatively concentrated conditions (e.g., 10-50 wt%) with varied solvent systems, such as water, alcohol, ethylene glycol, etc. [START_REF] Derry | Polymerization-induced self-assembly of block copolymer nanoparticles via RAFT non-aqueous dispersion polymerization[END_REF][START_REF] D'agosto | RAFT-Mediated Polymerization-Induced Self-Assembly[END_REF][141][142][143][144][145][146][147][148] Although a number of excellent reviews have demonstrated the importance of PISA techniques from perspectives of RDRP methods, [START_REF] Derry | Polymerization-induced self-assembly of block copolymer nanoparticles via RAFT non-aqueous dispersion polymerization[END_REF][START_REF] D'agosto | RAFT-Mediated Polymerization-Induced Self-Assembly[END_REF]142,143 polymerization techniques, 141, 144 mechanisms, [139][140][141] and others, [145][146][147][148] (above 73-75% vs 55-66%). [START_REF] Xu | Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT[END_REF] F NMR characterizations indicate that the dispersion polymerization progresses through monomer-swollen micelles formed with block copolymers. In the same year, the same group 151 further adopted diblock copolymers of poly(MAA)-b-poly(benzyl methacrylate) (poly(MAA)-b-poly(BzMA)) with trithiocarbonate terminals as macro-CTAs in the RAFT-mediated PISA in ethanol (Scheme 13). As the TFEMA conversion gradually increases, the morphologies of FPNPs evolve from spheres to worms and finally vesicles as evidenced by TEM.

When highly hydrophilic poly(glycerol monomethacrylate), poly(GMA), capped with dithiobenzoate as a macro-CTA for chain-extension was adopted by Armes and co-workers, the PISA approach allowed the preparation of FPNPs with poly(TFEMA) cores via aqueous emulsion RAFT polymerization. 153 DPs of both poly(GMA) and poly(TFEMA) showed an apparent impact on the particle size, facilitating diameter regulation (20 to 250 nm by TEM) by optimizing the length of two blocks (Figure 9). This method presents a useful pathway to yield FPNPs of low PSD (typically < 0.10) at 20 wt% solid contents in water. Later, Czajka and Armes 154 reported the employment of time-resolved small-angle X-ray scattering (SAXS) in aqueous emulsion polymerization of TFEMA using a persulfate initiator, and disclosed that TFEMA was more favorable than styrene for the purpose of in situ SAXS, due to the greater X-ray scattering contrast as compared to water. Although this contribution is not for the formation of FPNPs based on RDRPs, the temporal characterization technique could be further used to provide useful insights into the mechanism of PISA process with fluorinated (meth)acrylates. Copyright 2018 American Chemical Society.

In 2018, An and co-workers 162 demonstrated the synthesis of diblock copolymers using poly(17FDMA) as the second block by chain-extension from a variety of macro-CTAs under thermal conditions, yielding FPNPs of fusiform, vesicle, rod-like, tube-like morphologies via PISA process (Figure 11). Although poly(17FDMA) possesses very low solubility in most solvents, and could cause precipitation during chain-growth, this robust dispersion polymerization enables direct access to diblock copolymers with poly(17FDMA) segments at high concentrations and with quantitative 17FDMA conversions. Obtained FPNPs show excellent dispersibility in many organic solvents, such as acetone, acetonitrile, ethyl acetate, dioxane, dimethyl sulfoxide (DMSO), dimethylformamide, dichloromethane, toluene, etc., which could expand their applicable scope. In 2020, Chen and co-workers 173 reported a macro-CTA differentiation strategy, which enables the controlled synthesis of ultra-high-molecular-weight (UHMW, Mn > 10 6 Da) polymers using fluorinated (meth)acrylates (e.g., 9FHMA, nonafluorohexyl acrylate (9FHA), dodecafluoroheptyl methacrylate (12FHMA)) and acrylamides (e.g., nonafluorohexyl methacrylamide) in chainextensions under visible-light irradiation conditions. In comparison to conventional RDRPs, where all CTAs are supposed to be consumed in chain-growth, the macro-CTA differentiation strategy involves a more complex polymerization process as disclosed by kinetic investigation 173,174 and machine-learning assistance. 175 The chain-growth of ultra-long solvophobic fluorinated blocks onto non-fluorinated solvophilic macro-CTA (e.g., poly(DMA), poly(MMA)) generates spherical FPNPs (Dh ≈ 80-280 nm by DLS) of low PSD (<0.14) and with up to 50 wt% solid contents in DMSO.

However, when this reaction was conducted at elevated temperature (e.g., 70 ⁰C) with AIBN initiator via RAFT polymerization, all macro-CTAs were consumed to provide polymers of regular molar masses, without the detection of macro-CTA differentiation, revealing that the mild reaction conditions should be crucial to afford UHMWs in this system.

ACS Paragon Plus Environment

Submitted to Chemical Reviews interaction, fluorophilic/ionic interaction). Alternatively, the PEG-based macroinitiator could be replaced by poly(MMA) capped with alkyl chloride in the Ru-catalyzed RDRP, which has further allowed the preparation of FPNPs in organic solvents and with a variety of fluorinated methacrylates bearing 9 to 17 fluorine atoms in each monomer. 189,190 Scheme 17. Schematic illustration for the synthesis of functional cross-linked FPNPs based on Rucatalyzed polymerization. 188 Chen and co-workers [START_REF] Quan | Fluorous-Core Nanoparticle-Embedded Hydrogel Synthesized via Tandem Photo-Controlled Radical Polymerization: Facilitating the Separation of Perfluorinated Alkyl Substances from Water[END_REF] developed photoredox-mediated RAFT polymerization of nonafluorohexyl methacrylamide or perfluorooctyl methacrylamide using ethylenedimethacrylamide as a cross-linker, phenothiazine derivative as a photocatalyst, PEG substituted trithiocarbonate as a CTA, under visible-light irradiation in ethanol. This method not only provides cross-linked FPNPs of high fluorine concentrations in cores and narrow particle size dispersity (e.g., PSD = 0.140, Dh = 25 nm by DLS), but also avoids metal-contamination concerns by using organic photocatalyst and improves chemical stability by introducing methacrylamidebased fluorinated monomers. The observations of remaining macro-CTA and the high-molar-mass fluoropolymers (up to about 10 6 Da) are in accord with findings in their previous works. [173][174][175] Taking advantage of the remaining macro-CTA and PC in a solvent, as well as trithiocarbonate functionalized FPNPs, when the reaction mixture was treated with additional acrylamide, ethylenedimethacrylamide and water under light irradiation, FPNPs-embedded hydrogels were produced at quantitative yields, which was further examined for PFASs adsorption (section 5.5).

GRAFTING FROM INORGANIC NANOPARTICLES VIA RDRPS

Inorganic-polymeric core-shell nanohybrids have served as robust platforms to provide highperformance nanostructured materials. [191][192][193] The large surface energy of nanoparticles inevitably causes the formation of aggregates in the polymer matrix, which exhibit many negative impacts on Takahara and co-workers 200,201 developed SI-ATRP of (meth)acrylates using different surfaces and particles as substrates. The use of fluoroalcohol solvents allows controlled chain-growth of ionic monomers with copper catalysts. In 2013, Ma, Yang and co-workers 199 reported the preparation of nanocomposites poly(13FOMA)@BaTiO3 based on SI-ATRP (Figure 14a), yielding hybrid FPNPs of 30-50 nm inorganic cores and about 5 nm polymeric shells (Figure 14b). The synthetic process includes two stages: (i) the modification of BaTiO3 nanoparticle surface via a sequence of hydroxylation, silylation and amidation to yield BaTiO3 nanoparticles linked with alkyl bromide as initiating sites; (ii) the synthesis of core-shell structured poly(13FOMA)@BaTiO3 nanoparticles through grafting from modified BaTiO3 surface. Different ratios of BaTiO3/13FOMA

were utilized to probe the influence on dielectric properties. The results demonstrated that increasing the BaTiO3 content is favorable to achieve a high dielectric constant (up to 7.4 at 100 kHz at room temperature) and reducing dielectric loss, which is of interest to high energy storage devices (section 5.4).

In 2014, He's group 202 prepared fluorinated diblock copolymers grafted onto silica particles via SI-ATRP of MMA and 12FHMA. Nanohybrids of SiO2-g-poly(MMA)-b-poly(12FHMA) were synthesized with 25-30 nm spherical core-shell nanoparticles from 10-25 nm silica particles as observed by TEM. In comparison to poly(MMA)-b-poly(12FHMA) diblock copolymers obtained by ATRP, the diblock copolymer shells grafted from silica nanoparticles are favorable to increasing the surface roughness of films, which can promote the hydrophobic and oleophobic properties.

Grafting from Inorganic Nanoparticles via RAFT Polymerization

In 2018, Zhang, Luo and co-workers 203 demonstrated the synthesis of novel rigid liquidcrystalline fluoropolymers of poly [2,5-bis[(4-trifluoromethoxyphenyl)oxycarbonyl]styrene],

poly(TFMPCS). It enables the preparation of a series of core-shell structured poly(TFMPCS)@BaTiO3 via SI-RAFT with different thicknesses of interfacial layers. The shell thickness could be regulated by modulating the degree of polymerization of TFMPCS. The introduction of poly(TFMPCS) shell layer onto BaTiO3 surface improved the affinity with poly(VDF-TrFE-CTFE) as a matrix. The poly(TFMPCS)@BaTiO3/poly(VDF-TrFE-CTFE) nanohybrid films were fabricated via solution blending. The dielectric behavior and energy storage capacity were probed to explore the potentials for energy storage purpose (section 5.4).

In 2019, Ameduri's group 204 reported the fabrication of inorganic-polymeric core-shell particles using VDF for the first time, yielding PVDF-g-BaTiO3 nanohybrids via SI-RAFT of VDF from surfacefunctionalized BaTiO3 nanoparticles (Figure 14a). The ceramic nanoparticles were surfacemodified to connect with xanthate groups as CTAs, which ensured the grafting of PVDF from the modified BaTiO3 surface. Decreasing the BaTiO3 concentration from 20 wt% to 5 wt% led to the thickness of polymer shell varying from 2.2 nm to 5.1 nm. Authors demonstrated that high BaTiO3 loading tends to improve the thermal stability of the nanomaterials and reduce their crystallinity rate.

APPLICATIONS

Since the last century, FPNPs have been broadly applied for coatings, paintings, additives, membranes and other purposes in construction, automobile, aerospace, chemical industries and so on. [START_REF] Ebnesajjad | Introduction to Fluoropolymers: Materials, Technology, and Applications[END_REF][START_REF] Scheirs | Modern Fluoropolymers: High Performance Polymers for Diverse Applications[END_REF][START_REF] Améduri | Applications[END_REF] Advancements in RDRPs have brought FPNPs with customized functionalities, fluorine densities, morphologies, sizes, solubilities, mechanical strength and other desirable properties, which have allowed their increasing investigations for high-tech applications. This section will highlight the emerging applications of FPNPs afforded based on RDRPs in recent years, which include [START_REF] Xu | Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT[END_REF] F MRI, biomedical delivery, energy storage, PFASs adsorption, photosensitizer and others.

Magnetic Resonance Imaging

MRI is one of the most useful clinical imaging techniques, attributed to the noninvasive property and high versatility that facilitates in-situ investigations of physiological, anatomical information. 205- 207 19 F MRI allows unambiguous detection of fluorine signals with negligible background influence from the human body, and [START_REF] Xu | Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT[END_REF] F nucleus possesses 100% natural abundance with satisfactory resonance frequency (versus about 94% of 1 H nucleus) and magnetic resonance sensitivity (versus about 83% of 1 H nucleus). 208,209 The strong C-F bonds provide outstanding bio-inertness for fluorocarbons. As a result, [START_REF] Xu | Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT[END_REF] F MRI has been developed as a powerful and visualizable technique which provides independent and complementary information for biological and clinical imaging applications. 210,211 Various fluorine-containing imaging agents have been designed, including small molecules, macromolecules and FPNPs, as well as paramagnetic metal-based substances. 212

Among them, FPNPs are able to provide high fluorine density, tunable circulation time, stimulus responsiveness, and therefore have received considerable attention. This section highlights examples of applying FPNPs in [START_REF] Xu | Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT[END_REF] F MRI investigations. Equation 1In MRI, imaging intensity (I) depends on various parameters as N(F) represents the [START_REF] Xu | Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT[END_REF] F atoms that are detectable by NMR, TR is pulse sequence repetition time, and TE is echo delay time (Equation 1) . 213 To afford high imaging intensity in [START_REF] Xu | Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT[END_REF] F MRI, high spin-spin relaxation time (T2) and low spin-lattice relaxation time (T1) are favorable according to this equation, where an increase of T2 causes enhanced signal-to-noise ratio, and a decrease of T1 declines scan time. The relaxation time of T2 parameter is dictated by dipolar coupling of the [START_REF] Xu | Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT[END_REF] F nuclei with nearby [START_REF] Xu | Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT[END_REF] F/ 1 H nuclei.

Therefore, T2 can be influenced by the spatial distribution of [START_REF] Xu | Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT[END_REF] F/ 1 H and their relative mobility. 185,213 Fluorine contents can cause different extents of influences on T1 and T2, as demonstrated by FPNPs obtained via solution self-assembly, PISA and covalent cross-linking processes. 166,185,186 For nano-objects of spherical, worm-like and vesicle morphologies, T1 and T2 remain constant, indicating no dependence of relaxation time on morphology, and implying that architectures and dynamics of hydrophilic shells of FPNPs are not detectably altered for those nano-objects. 166 In comparison, using Chinese Hamster Ovarian (CHO) cells as an example, authors illustrated that morphology exhibited an apparent impact on cell uptake, 166 where worm-like FPNPs showed the highest uptake, and those FPNPs exhibited little or no cytotoxicity. 17c). 230 The outstanding penetration into tumors implies that such PFPE-based particles could be potentially useful for both diagnosis and treatment of diseases. Moreover, the thiol groups on FPNPs are versatile functional groups to connect with other functional molecules to facilitate multiple imaging purposes. 231

Biomedical Delivery

In past decades, a variety of substances such as nanomaterials, polymers and lipids have been explored as candidates for biomedical delivery. [START_REF] Lv | Fluoropolymers in biomedical applications: state-of-the-art and future perspectives[END_REF]232 However, problems including biocompatibility, transfer efficiency, carrying ability and others have hindered practical applications of many candidates. To address such difficulties, rationally designed FPNPs of tunable water solubility have been disclosed as promising materials for biomedical delivery (e.g., gene, protein and drug delivery), providing fruitful results as summarized in several excellent reviews. [START_REF] Lv | Fluoropolymers in biomedical applications: state-of-the-art and future perspectives[END_REF][232][233][234][235] Although most studies are based on FPNPs prepared via conventional organic reactions, for example, modifications of macromolecules with fluorinated small-molecular agents (e.g., perfluorinated anhydride, perfluorinated carboxylic acid, perfluorinated acyl chloride, etc.) via amidation, esterification and others, [START_REF] Lv | Fluoropolymers in biomedical applications: state-of-the-art and future perspectives[END_REF][232][233][234][235] RDRPs present an alternative pathway that allows customized access to FPNPs with readily available starting materials. In this section, advantages of fluoropolymers in related applications will be discussed, and studies of gene, protein and drug deliveries with FPNPs prepared based on RDRPs will be highlighted.

Gene Delivery

The utilization of genes as therapeutic agents to recover defective production of proteins, regulate gene expression holds great potentials for the treatment of both heritable and acquired diseases. 235 However, the lack of effective carriers has largely restricted the usage of genetic therapeutics. A successful gene carrier should provide protection to genes, avoid detection/clearance, prevent undesirable interactions with non-target proteins/cells, selectively release genes after overcoming various barriers, meanwhile, maintain non-toxicity during the whole process. In addition, nucleic acids are normally negatively charged. Lots of developments have used cationic polymers as carriers to form nanoscale complexes with genes, namely, polyplexes, via electrostatic interactions. [235][236][237] Because of the abundant presence of salts, serum proteins and other polyanions in the physiological environment, lots of polyplexes with genes are lack of enough stability, leading to the usage of higher amounts of cationic carrying materials, which could simultaneously bring risks of destroying cell membranes, causing inflammation, etc. 238 To address such problems, researchers have developed fluorinated polymeric carriers. 239 Thanks to the strong hydrophobic and fluorophilic properties, fluorinated segments connected on the cationic polymers could stabilize polyplexes in physiological environments at low critical concentrations, defending them from destabilized by serum proteins and other negatively charged biomacromolecules. [239][240][241][242][243] At the same time, while fluoropolymers have shown bio-inert and antifouling properties, fluorinated polyplexes have exhibited improved serum tolerance without decreasing transfection efficiency. [244][245][246][247][248] To deliver nucleic acids such as DNA, siRNA, miRNA, etc., synthetic modifications of polyamidoamine, poly(ethylenimine), poly(propylenimine), poly(amino ester), polypeptides and many other dendrimers with fluorinated agents have been developed to produce cationic fluorinated carriers.

To expand the fluoropolymer scope for the transduction of nucleic acids, Zentel and co- Since intracellular gene delivery should interact with several liquid-solid interfaces including membranes of cell, endosomal and nuclear, investigations on the dynamics of polymer kinetics on the related interfaces are important for the design of polymer carriers. [235][236][237] Higgins, Iyer and coworkers 252 prepared linear random copolymers via ATRP and post-functionalized copolymers with azide side groups. Poly(amidoamine) dendrons were grafted onto the linear backbone via click reaction between azide and alkyne functional groups, followed by post-modification of poly(amidoamine) with perfluorinated anhydride. This protocol allows the regulation of molar masses, charge density on the dendronized linear polymeric topology. As assisted by high-speed AFM, authors systematically probed polymer dynamics (velocity, displacement, diffusion) under physiologically related conditions, and demonstrated that the interaction strength and diffusion performance with fluorinated polyplexes are relevant to the transfection potential.

Protein Delivery

Proteins are capable of acting precisely on targets and regulate biological processes with outstanding selectivity and potency, providing protein-based therapeutics with high specificity and low adverse effects as compared to small-molecule drugs. [253][254][255] Despite the merits, protein-based therapeutics encounter significant obstacles posed by in vitro and in vivo instability. The rational design of suitable carriers, which can shield proteins from enzymatic degradation and prolong retention of proteins without introducing cytotoxicity, is a painful task due to the intrinsic characteristics of proteins, such as indeterminate charge properties depending on the isoelectric point and environmental pH value. 256 The limited negative charges on proteins are the major barrier to mimicking gene delivery, which adopts cationic polymers as carriers. Unstable protein-carrier complexes will disassemble in the presence of salts, polyanions and phospholipids in corresponding bio-environmental conditions. [257][258][259][260] To address these issues, two approaches have been developed, including a) fabrication of protein-polymer conjugates via dynamic covalent linkages, b) improving binding affinity between polymeric carriers and proteins via synthesis of welldefined functional polymers or chemical modifications of proteins. 255 While current protein drugs are frequently restricted to extracellular targets due to the limited membrane permeability of proteins, 261 intracellular protein delivery has drawn considerable attention in recent years. For this purpose, fluorinated polymers and oligomers are promising candidates as delivery carriers for proteins, particularly for intracellular protein delivery. 260 The hydrophobic and lipophobic properties endow fluoropolymers with high efficiency of transporting across cell membranes, because hydrophobicity facilitates membrane association, and lipophobicity prevents blending with phospholipids on cellar membranes. [START_REF] Lv | Fluoropolymers in biomedical applications: state-of-the-art and future perspectives[END_REF] The restricted fusion of

Drug Delivery

Although chemotherapy provides an essential approach for cancer treatment, problems in drug delivery, such as poor water solubility and physiological barriers, decrease the efficacy. 264,265 Meanwhile, normal cells are prone to be influenced by free drugs, causing toxicity to patients.

Suitable drug delivery systems, especially with nanoparticles as carriers, are promising to overcome these issues. The drug-nanoparticle combined systems are able of reaching increased drug solubility, providing protection for drugs from quick clearance, allowing sustained drug release Page 39 of 71 ACS Paragon Plus Environment Submitted to Chemical Reviews and minimizing side effects. [265][266][267] Typical nanocarriers include PNPs, inorganic nanoparticles and liposomes. Among them, PNPs are able to furnish good tunability for the drug release process based on their remarkable structural versatility. 268 To this end, fluoropolymers display desirable attributes in several aspects, including 1) excellent self-assembly and self-folding behaviors that can enhance the stability of complexes, 2) good integration of drug carrying and in vivo imaging that can combine diverse functions within a uniform system, 3) improved endocytic efficiency that can optimize therapeutic efficacy. [START_REF] Lv | Fluoropolymers in biomedical applications: state-of-the-art and future perspectives[END_REF]269,270 Reproduced with permission from ref 269 . Copyright 2020 American Chemical Society.

Photosensitizer

Photodynamic therapy (PDT) is a non-invasive and practical treatment for cancers and nonmalignant diseases. 273 Photosensitizers (PSs) employed in PDT can be activated by visible-light irradiation, enabling energy transfer to ground-state oxygen ( 3 O2) to generate singlet oxygen ( 1 O2).

The photo-excited oxygen can destruct tumor cells via apoptosis and/or necrosis, affect tumor vasculature that can induce tumor hypoxia and starvation. 274 In comparison to conventional therapies, PDT displays many merits relevant to its minimized invasive nature, dual specificity depending on both PSs accumulation and light delivery at the lesion location, as well as the capability of repeating treatment without initiating resistance. 275,276 However, the therapeutic efficacy of PDT is limited by the solubility of PSs and the availability of oxygen within tissues.

Owing to the hydrophobic property, many PSs are prone to aggregate in aqueous solutions, thus causing insufficient tumor uptake and quenching photosensitivity, severely. Although a variety of delivery systems, especially nanoparticles, have been developed to improve the water solubility of PSs, PS-located cores become the major hindrance to oxygen diffusion. At the same time, the PDT process is oxygen-dependent. Photosensitization will not occur in anoxic areas of tissues.

While the pathophysiological property of hypoxia has been observed in many solid tumors, hypoxia also arises from PDT-induced oxygen consumption and vascular damage. [START_REF] Que | Enhancing Photodynamic Therapy Efficacy by Using Fluorinated Nanoplatform[END_REF]277 Fluorocarbons exhibit good oxygen affinity, 233,234 which can solubilize much more oxygen than their hydrocarbon counterparts. 278 Based on the unique properties of fluorocarbon and merits of RDRPs, customized FPNPs are promising to combine desirable properties including good water solubility and efficient oxygen supply, relieving issues caused by the hypoxia microenvironment in tumor sites.

To investigate the influence of the content of fluorine on PDT, Huang and co-workers [START_REF] Que | Enhancing Photodynamic Therapy Efficacy by Using Fluorinated Nanoplatform[END_REF] synthesized spherical nanoparticles with different ratios of PFPMA to porphyrin within the core FPNPs. [START_REF] Liu | Sensitization of Hypoxic Tumor to Photodynamic Therapy via Oxygen Self-Supply of Fluorinated Photosensitizers[END_REF] Reproduced with permission from ref [START_REF] Liu | Sensitization of Hypoxic Tumor to Photodynamic Therapy via Oxygen Self-Supply of Fluorinated Photosensitizers[END_REF] . Copyright 2019 American Chemical Society.

Energy Storage

Dielectric materials with high dielectric constant and sufficient electric breakdown strength have drawn widespread interest owing to their broad potential applications in energy storage devices. 195,281,282 Energy density (Ue), a parameter for characterizing the storage capacity of dielectric materials, is defined as Equation 2for nonlinear dielectric materials: 203,[282][283][284] 𝑈 𝑒 = ∫ 𝐸 d𝐷 Equation 2where E represents the applied electric field, D represents the electric displacement. When it comes to linear dielectric materials, the energy density can be determined with Equation 3, High dielectric constants can be achieved with ceramic materials, particularly with BaTiO3.

𝑈 𝑒 =
However, the relatively low electric breakdown strength and processing difficulties of inorganic materials hinder their usage in many electronic devices. 195,285 In this regard, high electric breakdown strength can be achieved by merging with polymers, which meanwhile possess advantages of low dielectric loss, easy processing and low cost. 204,284,286 However, even for ferroelectric fluorinated polymers (e.g., PVDF and VDF copolymers ), which exhibit the highest dielectric constants (ε ∼10 at 1 kHz) among numerous polymers, 115,124,287,288 their blends with ceramic materials often afford poor performance as limited by processing techniques. The high surface energy and large specific surface area of ceramic nanoparticles cause aggregation in the polymer matrix, giving rise to electron conduction with considerable dielectric loss, poor breakdown strength and other deteriorated electrical properties. To achieve homogeneous nanoparticle dispersion, surface modification of ceramic nanoparticles based on "grafting from" strategy (section 4) has been shown as powerful tools. 195,289 Based on the low surface energy of fluoropolymers, Ma, Yang and co-workers 199 prepared poly(13FOMA)@BaTiO3 nanocomposites via SI-ATRP reaction (Figure 14). The intrinsic nature of C-F bonds is beneficial to decrease the polarization of materials. Authors revealed that poly(13FOMA)@BaTiO3 nanohybrids not only increased the dielectric constant, which is almost three times poly(13FOMA), but also significantly reduced the dielectric loss.

When employing SI-RAFT polymerization, this technique avoids metal-contamination concerns in polymer synthesis process, which is favorable to preventing high leakage currents under high electric fields. 289 In 2018, Zhang, Luo and co-workers 203 fabricated core-shell structured PTFMPCS@BaTiO3 via SI-RAFT (Figure 14), and blended these nanohybrids with poly(VDF-TrFE-CTFE) matrix. This work demonstrates that the shell thickness affects the dielectric constant, breakdown strength and energy density. When the shell thickness was approximately 11 nm in nanocomposites containing 5 vol% BaTiO3, the energy density was up to 16.18 J cm -3 , providing useful information for further engineering of high-energy-density dielectric material.

With PVDF@BaTiO3 made via SI-RAFT polymerization, 204 Raihane et al. 289 reported that the core-shell FPNPs provide enhanced dielectric permittivity of about 50% higher than the prediction of the nanocomposite based on the Maxwell Garnett dielectric model, suggesting the promising PVDF/BaTiO3 interface achieved by "grafting from" polymerization.

Per-and Polyfluoroalkyl Substances Adsorption

PFASs represent a family of synthetic chemicals that are broadly used as surfactants, water and oil repellents, fire retardants in industrial and consumer products (>200 applications) for many decades. [290][291][292] In recent years, researchers found that PFASs show high persistence in the environment (e.g., different water sources including lakes, rivers, underground water as well as inland seas and oceans) and a tendency to bio-accumulate. 293 Rodent and human studies have identified adverse effects associated with PFAS exposure. 294 Many national, regional regulatory agencies and organizations have already restricted the use of several PFASs, especially, perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS) and perfluorononanoic acid (PFNA).

In contrast to low-molar-mass PFASs which are water-soluble, mobile, persistent, bioaccumulative and toxic, fluoropolymers are safe, bioinert, non-toxic, non-bioaccumulative and insoluble in water. 290,295 In addition, approximately 96% of fluoropolymers fulfill the "Polymer of Low

Concern" (PLC) criteria 296, 297 defined by Organization for Economic Cooperation and Development Beyond FPNPs, researchers also developed other fluorinated sorbents as outstanding host molecules for PFASs guests. For example, cross-linked fluoropolymer gels 301, 306 β-cyclodextrinbased polymers, 307 granular activated carbon 308 are demonstrated as highly efficient polymeric materials to capture neutral and/or anionic PFASs. The "smart" performance of those fluoropolymers further highlights that the fluorophilicity effect could be utilized as a fundamental principle to promote PFASs adsorption toward a sustainable society.

Others

Apart from above-mentioned applications in the fields of MRI agents, biomedical carriers, energy storage and PFASs removal, FPNPs have also gained considerable interests in other applications. Because we only found a few studies for each direction that benefits from FPNPs prepared via RDRPs, related examples are introduced below.

Thanks to the hydro-oleophobicity and extremely low surface energies of fluoropolymers, especially those bearing a perfluorinated side chain, nano-structural fluorinated coatings provide an important foundation for the design of superhydrophobic surfaces (water contact angle (WCA) above 150° and water droplet roll-off angle (RoA) below 10°), which are capable of self-cleaning, anti-fouling and anti-bacterial. [START_REF] Lv | Fluoropolymers in biomedical applications: state-of-the-art and future perspectives[END_REF]309 Superhydrophobic surfaces are normally prepared through the integration of surface roughness and low surface energy materials. However, surface roughness reduces transparency owing to increased light scattering, which causes hindrance to the fabrication of transparent superhydrophobic coatings. 310 For this problem, Detrembleur and co-workers 311 prepared amphiphilic fluorinated block copolymers of 17FDMA, which form FPNPs via a PISA process. After a thermal treatment to promote chain movement and film reorganization, the fluorinated blocks migrated from the core of FPNPs to the film-air interface, providing hydrophobic coatings. When blending FPNPs with silica nanoparticles to improve surface roughness, superhydrophobic coatings (WCA = 153 °, RoA < 2 °) with high transparency were successfully formed.

PNPs formed by block copolymers are important stabilizers for the formation of Pickering emulsions, which are surfactant-free, kinetically stabilized dispersions of two immiscible liquids. 312 Motivated by environmental reasons, Pickering emulsions have attracted many interests to mitigate the adoption of surfactants and organic solvents, and found applications across different industrial processes. 312 An and co-workers 162 synthesized FPNPs of diverse surface wetting properties based on RAFT polymerization, and explored their behaviors as Pickering stabilizers for solvents of a broad range of polarity. Pickering emulsions of both oil-in-water and oil-in-oil systems were prepared using commonly used toluene, DMF, DMSO as organic solvents, showcasing the versatility and robustness of the fluoropolymers. Notably, in many examples, block copolymers are cross-linked to prevent the break of emulsions, and a large number of surfactants are required to form high internal phase emulsions. In sharp contrast, this system avoids complicated synthesis and enables the emulsion formation with up to 80% of the internal phase.

While ultrasound is broadly applied as a clinical imaging technique, 313 it is still limited by the lack of robust contrast agents to improve the distinction among different tissues. 314 The fast diffusion of gas encapsulated in conventional ultrasound contrast agents lead to short circulation time. To provide stable nanosized ultrasound contrast agents, Tsapis and co-workers [START_REF] Houvenagel | Comb-Like Fluorophilic-Lipophilic-Hydrophilic Polymers for Nanocapsules as Ultrasound Contrast Agents[END_REF] prepared triblock copolymers of PEG-polylactide-poly(17FDMA). In comparison to PEG-polylactide nanocarriers, the FPNPs provide a 2-fold increase in the encapsulation efficiency for perfluorooctyl bromide. The FPNPs afford a higher in vitro ultrasound signal than that of PEG-polylactide nanocarriers, and exhibit insignificant in vitro cytotoxicity. derivatives as repeating units. Consequently, the synthesis and applications of FPNPs mainly focus on such polymeric structures. To polymerize gaseous fluoroalkenes (e.g., TFE, VDF, CTFE), [START_REF] Ebnesajjad | Introduction to Fluoropolymers: Materials, Technology, and Applications[END_REF][START_REF] Scheirs | Modern Fluoropolymers: High Performance Polymers for Diverse Applications[END_REF][START_REF] Améduri | Applications[END_REF][START_REF] Améduri | Fascinating Fluoropolymers and Their Applications[END_REF][START_REF] Smith | Handbook of Fluoropolymer Science and Technology[END_REF][START_REF] Hougham | Fluoropolymers: Synthesis and Applications[END_REF]115 which are largely manufactured in industries, conventional techniques highly rely on high-pressure metallic autoclaves. Although ITP that is the oldest and RAFT polymerization are promising to afford main-chain fluoropolymers of complicated compositions and structures, the high-pressure operations at elevated temperatures and limited controllability could be challenging to realize on- sequences with a broad scope of comonomers, though the scaling-up ability has yet to be promoted. [START_REF] Zhou | Main-Chain Fluoropolymers with Alternating Sequence Control via Light-Driven Reversible-Deactivation Copolymerization in Batch and Flow[END_REF][START_REF] Zhao | Controlled radical copolymerization of fluoroalkenes by using light-driven redox-relay catalysis[END_REF][START_REF] Jiang | Photoorganocatalyzed Reversible-Deactivation Alternating Copolymerization of Chlorotrifluoroethylene and Vinyl Ethers under Ambient Conditions: Facile Access to Main-Chain Fluorinated Copolymers[END_REF][START_REF] Quan | Visible-Light-Enabled Organocatalyzed Controlled Alternating Terpolymerization of Perfluorinated Vinyl Ethers[END_REF] Meanwhile, continuous-flow polymerizations have been shown as a striking technique to promote polymerization without losing control over chain-growth, and are useful to facilitate manipulation of gaseous and low-boiling-point monomers via precise in-line regulation and computer-aided programmable operation. 315,316 We anticipate that those novel synthetic approaches and platforms will be quite interesting to promote the bottom-up engineering of novel FPNPs with fluoropolymers of a broader monomer scope, larger sequence and topological scopes.

CONCLUSION AND FUTURE PERSPECTIVES

Second, despite morphologies playing an important role in influencing the properties of FPNPs, it has been rarely possible to access diverse morphologies with each strategy, and complicated nanostructures are quite limited. In order to obtain diversified morphological FPNPs, various strategies have been explored through the integration of solvophilic and solvophobic segments along the macromolecular backbone based on RDRPs, where each strategy presents different scopes of morphologies. For example, with the PISA strategy, nano-objects including spheres, worms, cylinders, vesicles, raspberry-like particles, sponge-like particles, even cubosomes, have been produced via thermal or photo-induced chain-extension polymerization from solvophilic macro-initiators/CTAs. In comparison, with the single-chain folding and cross-linking polymerization strategies, spherical FPNPs are normally afforded, where more complicated morphologies are hardly observed so far. It is still difficult to provide comparable scopes of FPNPs with different strategies. Because many applications highly depend on size, stability, concentration of FPNPs, which are synthetic characteristics of different methods, it will be useful to expand the FPNPs scope for each avenue. Moreover, emerging studies have disclosed that multicomponent PNPs could be achieved by complex sequences. 111,112,163 However, fluoropolymers with complex sequences and suitable solvophilicity/solvophobicity are extremely limited so far. It is highly desirable to further expand the scope of such fluoropolymers and explore their aggregation behaviors, which is important to elucidate the in-depth relationship between microstructures and properties.

Last but not least, compared to the vast applications of fluoropolymers in a broad range of areas, investigations with tailor-made FPNPs are still at the early stage. For example, well-defined fluoropolymers have been demonstrated as promising materials for solid polymer electrolytes 317,318 and protective coatings on electrodes 319 for the next-generation lithium batteries thanks to their electrochemical stability, [START_REF] Lopez | Designing polymers for advanced battery chemistries[END_REF] high-performance coatings for microelectronic purposes due to their thermal and chemical inertness, 320, 321 functional membranes for water purification and energy applications, 322,323 and others. In comparison, tailor-made FPNPs, especially for nanoparticles with morphologies other than spheres, have been rarely investigated toward such cutting-edge areas.

It will be interesting and fruitful to rational design FPNPs and expand their applications based on the outstanding behaviors demonstrated by well-defined fluoropolymers. However, it is difficult, even inaccessible for most scientists to handle both polymerization methods for FPNPs fabrication

Figure 1 .

 1 Figure 1. Schematic illustration for the formation of cross-linked FPNPs with poly(FSt)-bpoly(AA). 61 Reproduced with permission from ref 61 . Copyright 2001 John Wiley & Sons, Inc.

  prepared poly(styrene-r-acrylonitrile)-bpoly(tetrahydroperfluorooctyl methacrylate) (poly(St-r-AN)-b-poly(13FOMA)) via ATRP, which was employed as a stabilizer in the dispersion copolymerization of acrylonitrile and vinyl acetate in scCO2, affording spherical PNPs of Dn = 110-210 nm, particle size distribution (PSD) = 1.04-1.13.Topologically controlled polymers have been synthesized as building blocks for FPNPs.Wooley and co-workers 68 developed self-condensing vinyl polymerization based on Cu-catalyzed ATRP of 4-chloromethyl styrene, lauryl acrylate and tris(4′-(2′′-bromoisobutyryloxy)phenyl)ethane to yield hyperbranched star-like core capped with alkyl halide terminals (Figure2). Subsequent chain-extension polymerization allowed the grafting of 2,2,2-trifluoroethyl methacrylate (TFEMA) and tert-butyl acrylate (tBA) from the star-like macroinitiator via ATRP. The amphiphilic, hyperbranched star-like copolymers gave fluorinated micelles (Dh = 20-30 nm by dynamic light scattering (DLS)) that could be useful as nanoscopic magnetic resonance imaging (MRI) agents.Using alkyl bromides capped polyamidoamine dendrimers as a macroinitiator, the Ito group 69 demonstrated chain-extension polymerization using tetrafluoropropyl methacrylate and TFEMA as monomers via ATRP. Sizes (Dh) of FPNPs were controlled by molar mass of hyperbranched polymers in a range of 3-25 nm.

Figure 2 .Scheme 2 .

 22 Figure 2. Schematic illustration for the preparation of FPNPs with branched polymers prepared via ATRP.[START_REF] Du | Amphiphilic Hyperbranched Fluoropolymers as Nanoscopic 19F Magnetic Resonance Imaging Agent Assemblies[END_REF] Reproduced with permission from ref[START_REF] Du | Amphiphilic Hyperbranched Fluoropolymers as Nanoscopic 19F Magnetic Resonance Imaging Agent Assemblies[END_REF] . Copyright 2008 American Chemical Society.

Figure 3 .

 3 Figure 3. Cryo-TEM micrographs of micellar aggregates prepared with triblock copolymers of a) hydrophilic-lipophilic-fluorophilic sequence, b) lipophilic-hydrophilic-fluorophilic sequence. 92Reproduced with permission from ref[START_REF] Skrabania | Synthesis of Ternary, Hydrophilic-Lipophilic-Fluorophilic Block Copolymers by Consecutive RAFT Polymerizations and Their Self-Assembly into Multicompartment Micelles[END_REF] . Copyright 2010 American Chemical Society.

Scheme 4 . 94 Scheme 5 .

 4945 Scheme 4. Synthesis of amphiphilic homopolymer via RAFT polymerization.[START_REF] Liu | Construction of well-defined difluoromethylthiocontaining amphiphilic homopolymers by RAFT polymerization[END_REF]

97 Scheme 6 .

 976 Scheme 6. Synthesis of multi-responsive block copolymers via RAFT polymerization and postamidation.[START_REF] Kolouchova | Thermo-and ROS-Responsive Self-Assembled Polymer Nanoparticle Tracers for 19F MRI Theranostics[END_REF]

  . Due to the gaseous property of VDF, high-pressure metallic vessels were required to prepare the poly(VDF)-based macroinitiator under thermal and radical conditions. The amphiphilic poly(VDF)-b-poly(vinyl alcohol) [poly(VDF)-b-poly(VA)] block polymer was formed via hydrolysis of the poly(VAc) block, which self-assembled into spherical micelles of Dh = 147 (by DLS) in water, with the observation of minor particle aggregation.

Figure 4 .

 4 Figure 4. Schematic illustration for a) synthesis of the poly(VDF)-b-poly(VA) block copolymer via RAFT polymerizations and hydrolysis, b) and c) cryo-TEM micrographs of self-assembled FPNPs

Figure 5 .Scheme 7 .

 57 Figure 5. a) Degradative chain transfer onto PEG chains and following reactions. Cryo-TEM micrographs of self-assembled FPNPs prepared in the presence of b) PEG-OH and c) macro-CTA.[START_REF] Fuentes-Exposito | Surfactant-free emulsion polymerization of vinylidene fluoride mediated by RAFT/MADIX reactive poly(ethylene glycol) polymer chains[END_REF] Reproduced with permission from ref[START_REF] Fuentes-Exposito | Surfactant-free emulsion polymerization of vinylidene fluoride mediated by RAFT/MADIX reactive poly(ethylene glycol) polymer chains[END_REF] . Copyright 2021 Royal Society of Chemistry.

Scheme 10 .

 10 Scheme 10. Synthesis of block copolymers from the poly(St) macro-initiator based on NMP.129

Scheme 11 .

 11 Scheme 11. Schematic illustration of the single-chain folding with poly(St)-b-poly(DMA)-bpoly(PFSt) prepared by RAFT polymerizations. 135

Figure 6 .

 6 Figure 6. Synthesis and self-folding of amphiphilic fluorinated random copolymers. 136 Reproduced with permission from ref. 136 Copyright 2016 American Chemical Society.

Figure 7 .

 7 Figure 7. a) Single-chain folding of amphiphilic random copolymers with urea units. b) DLS intensity size distribution of copolymers with different sequences. 137 Reproduced with permission from ref 137 . Copyright 2016 American Chemical Society.

Figure 8 .

 8 Figure 8. Molecular dynamics simulations for the formation of self-folded single polymer chains in water and chloroform. 138 Reproduced with permission from ref 138 . Copyright 2018 Elsevier Ltd.

  it still lack of summary for the preparation of FPNPs based on PISA processes. Currently, the vast majority of PISA examples for the FPNPs synthesis are based on RAFT polymerization under thermal conditions. Recently, examples demonstrate that photo-mediated RDRPs (e.g., photoinduced electron/energy transfer (PET)-RAFT polymerization 149, 150 ), ATRP and cobalt-mediated RDRP could also be adopted for PISA. Semi-fluorinated (meth)acrylates and acrylamides, PFSt have been shown as useful fluorinated monomers for RDRP-based PISA processes. Analogous to PISA of non-fluorinated block copolymers, monomer concentration, degrees of polymerization (DPs) for different blocks and other parameters can implement impacts on morphologies of FPNPs, leading to fluorinated nano-objects of diverse morphologies including spheres, worms, vesicles and many more, as exemplified below.

3. 1 . 1 PISA

 11 Scheme 13. Synthesis of diblock and triblock copolymers via RAFT polymerization and formation of FPNPs of different morphologies (e.g, sphere, worms, vesicles).151

Figure 9 .

 9 Figure 9. a) Chain-extension from macro-CTA via RAFT polymerization. b) TEM images of poly(GMA)-b-poly(TFEMA) block copolymers formed during the PISA process, where G and F represent GMA and TFEMA units, respectively. 153 Reproduced with permission from ref 153 .Copyright 2016 American Chemical Society.

Figure 10 .

 10 Figure 10. Synthesis of diblock copolymers by chain-extension via RAFT dispersion polymerization and PISA into FPNPs with different morphologies. 159 Reproduced with permission from ref 159 . Copyright 2018 WILEY.

Page 23 of 71 ACS

 71 Paragon Plus Environment Submitted to Chemical Reviews Moreover, by selecting different macro-CTAs as the first blocks, this approach successfully merges two blocks of distinctive properties. For example, hydrophilic/crystalline PEG and fluorophilic/crystalline poly(17FDMA) are combined in PEG-b-poly(17FDMA); hydrophobic/amorphous poly(MMA) and poly(17FDMA) are combined in poly(MMA)-bpoly(17FDMA). The broad attainable scope of amphiphilic block copolymers is promising as novel Pickering emulsifiers.

Figure 12 .

 12 Figure 12. a) Synthesis of poly(DMA)-b-poly(St-alt-PFSt) block copolymers via RAFT dispersion PISA process. b) Schematic illustration of morphological evaluation of FPNPs. c) and d) Representative SEM and TEM micrographs of cubosomes (scale bar = 200 nm). 163 Reproduced with permission from ref 163 . Copyright 2019 Nature Publishing Group.

Figure 13 .

 13 Figure 13. a) and b) Synthesis and schematic illustrations of raspberry-like FPNPs via a tandem photo-mediated polymerization. c) SEM and TEM micrographs of raspberry-like FPNPs. 176 Reproduced with permission from ref 175. Copyright 2020 Royal Society of Chemistry.

3. 1 . 3 PISAScheme 15 . 3 . 2 Scheme 16 .

 13153216 Scheme 15. Synthesis of poly(ionic liquid)s via sequenced cobalt-mediated PISA of various Nvinyl-3-alkyl-imidazolium comonomers.183

4 . 1 Figure 14 .

 4114 Figure 14. a) Preparation of fluoropolymer@BaTiO3 via SI-RDRPs. b) TEM micrograph. 199 Reproduced with permission from ref 199 . Copyright 2013 Elsevier.

Figure 15 .

 15 Figure 15. a) Ex vivo fluorescence images of organs for biodistribution of PFPE-b-poly(OEGA) copolymers. b) Simulated conformation of assemblies with P1 and P2 in solution. 214 Reproduced with permission from ref 214 . Copyright 2017 American Chemical Society.

Figure 16 .Figure 17 .

 1617 Figure 16. a) Schematic illustration of multi-functional hyper-branched polymers. b) MRI images of organs with unconjugated and folate-conjugated polymers. c) Fluorescence images of mice after injecting unconjugated and folate-conjugated polymers. 225 Reproduced with permission from ref 225 .Copyright 2014 American Chemical Society.

  Scheme 18. a) Synthesis of statistical and block fluorinated copolymers via RAFT polymerization. b) Mechanisms of copolymers of two sequences in gene delivery. 250 Reproduced with permission from ref 250 . Copyright 2018 Royal Society of Chemistry.

Scheme 19 .

 19 Scheme 19. Generation of the protein-FPNP conjugate via a cleavable disulfide linkage.[START_REF] Koda | Amphiphilic/fluorous random copolymers as a new class of non-cytotoxic polymeric materials for protein conjugation[END_REF] Reproduced with permission from ref[START_REF] Koda | Amphiphilic/fluorous random copolymers as a new class of non-cytotoxic polymeric materials for protein conjugation[END_REF] . Copyright 2015 Royal Society of Chemistry.

Scheme 20 .

 20 Scheme 20. Chemical Structures for the star-block copolymers and the loading of Doxorubicin (DOX) into FPNPs. 271 Reproduced with permission from ref 271 . Copyright 2008 American Chemical Society.

Figure 18 .Figure 19 .

 1819 Figure 18. One-pot synthesis via combining RAFT and enzymatic transacylation and postmodification toward multi-functional copolymers. The inset is a representative confocal laser scanning microscopy image of HeLa cells treated with fluoropolymer-DOX complexes. 272 Reproduced with permission from ref 272 . Copyright 2016 Royal Society of Chemistry.

  indicated that the increase of PFPMA content resulted in a greater amount of reactive oxygen species production, and caused improvement of PDT efficacy, because the fluorinated segments improve the solubility and diffusivity of oxygen. It was hypothesized that fixing porphyrins onto the polymer network is beneficial to reduce its aggregation and self-quenching of the photo-excited species.279 This work offers a versatile platform to obtain photosensitizer delivery carriers, potentiating PDT in various disease treatments.

Figure 20 .Scheme 21 .

 2021 Figure 20. a) Chemical structure of the fluoropolymer-PS conjugate (zinc porphyrin-copolymer). b1) and b2) Confocal micrographs, where b1) is B16F10 cell-only control and b2) is B16F10 cells incubated with zinc porphyrin-copolymer. c1) and c2) Representative live/dead images of B16F10 cells incubated with zinc porphyrin-copolymer, where c1) and c2) represents cells kept in dark and light, respectively. 280 Reproduced with permission from ref 280 . Copyright 2017 Royal Society of Chemistry.

(

  Scheme 22. Schematic illustration for the synthesis of FPNP-embedded hydrogel and investigation on PFASs adsorption.[START_REF] Quan | Fluorous-Core Nanoparticle-Embedded Hydrogel Synthesized via Tandem Photo-Controlled Radical Polymerization: Facilitating the Separation of Perfluorinated Alkyl Substances from Water[END_REF] Reproduced with permission from ref[START_REF] Quan | Fluorous-Core Nanoparticle-Embedded Hydrogel Synthesized via Tandem Photo-Controlled Radical Polymerization: Facilitating the Separation of Perfluorinated Alkyl Substances from Water[END_REF] . Copyright 2020 American Chemical Society.

FPNPs

  that merge properties of fluoropolymers and polymeric nanoparticles, are of great interests for a broad range of applications. While conventional paths toward FPNPs are limited to free radical polymerizations, researchers have made enormous efforts to synthesize well-defined fluoropolymers based on RDRPs, which have promoted the fabrication of FPNPs with controlled chemical compositions, versatile functional substituents, tunable sizes and diversified/complicated morphologies. Those synthetic avenues can be classified into several groups, including 1) selfassembly or self-folding of purified fluorinated copolymers into multi-chain aggregates or singlechain unimers in solvents, 2) direction formation of FPNPs through PISA or cross-linking during controlled radical chain-growth, 3) grafting from inorganic nanoparticles to yield covalently bonded FPNPs with inorganic cores. Inspired by those synthetic advancements, extensive studies toward applications have been carried out worldwide. The unique physical, chemical and biological properties of fluorine, as well as the ultra-low size, high specific surface area and other attributes of PNPs have enabled FPNPs as high-performance 19 F MRI agents, biomedical nano-carriers and PDT photosensitizers toward healthy problems, robust and selective sorbents for PFASs related to environmental issues, dielectric nanohybrids toward energy storage goals, superhydrophobic coatings and emulsifiers in laboratorial and industrial applications. Although investigations of FPNPs synthesis based RDRPs and their applications are growing into a booming stage, many challenges remain to be addressed. First of all, although RDRPs allow facile preparation of fluoropolymers, most examples are limited to side-chain fluorinated polymers with semi-fluorinated, (meth)acrylates, styrene

  demand access to fluoropolymers, particularly for non-experts in polymer synthesis. To address such issues, novel synthetic methodologies and techniques have yet to be developed. Recently, the development of photoredox-mediated RDRPs provides new opportunities to accomplish controlled polymerizations of fluoroalkenes, enabling tailoring main-chain fluoropolymers at ambient conditions with common Schlenk glassware and synthesizing many unprecedented

  Where ɛr, ɛ0 and Eb are the relative dielectric constant, vacuum dielectric constant and breakdown strength, respectively.203 According to Equation3, Ue can be enhanced by increasing the dielectric constant ɛr or/and Eb of the dielectric materials.282

	Submitted to Chemical Reviews	Page 44 of 71
	1 2	𝜀 𝑟 𝜀 0 𝐸 𝑏 2	Equation 3
	ACS Paragon Plus Environment

ACS Paragon Plus Environment Submitted to Chemical Reviews ACS Paragon Plus Environment Submitted to Chemical Reviews ACS Paragon Plus Environment Submitted to Chemical Reviews ACS Paragon Plus Environment Submitted to Chemical Reviews ACS Paragon Plus Environment Submitted to Chemical Reviews 50 and various analyzing/characterizing techniques (e.g., tools in biomedical, energy, environmental studies) for applications. Therefore, systematic developments toward practical applications will highly rely on cooperation between different laboratories. ACKNOWLEDGEMENTS This research was financially supported by the Science and Technology Commission of Shanghai Municipality and the Shanghai Pilot Program for Basic Research Fudan University 21TQ1400100 (no. 21TQ007), the NSFC (no. 22171051) and the State Key Laboratory of Molecular Engineering of Polymers.BA thanks CNRS and the French Fluorine Network (GIS). ACS Paragon Plus Environment Submitted to Chemical Reviews ACS Paragon Plus Environment Submitted to Chemical Reviews ACS Paragon Plus Environment Submitted to Chemical Reviews ACS Paragon Plus Environment Submitted to Chemical Reviews ACS Paragon Plus Environment Submitted to Chemical Reviews ACS Paragon Plus Environment Submitted to Chemical Reviews ACS Paragon Plus Environment Submitted to Chemical Reviews

ACS Paragon Plus Environment Submitted to Chemical Reviews ACS Paragon Plus Environment Submitted to Chemical Reviews