Sophie C Larnaudie

Ariane Peyret

Louis Beauté

Pierre Nassoy
email: pierre.nassoy@u-bordeaux.fr

Sébastien Lecommandoux
email: lecommandoux@enscbp.fr

Photo-polymerization induced polymersome rupture

Poly(butadiene)-b-poly(ethylene oxide) (PBut 2.5 -b-PEO 1.3 ) giant polymersomes were prepared using an emulsion-centrifugation method. The impact of a fast decrease of the osmotic pressure inside the lumen of giant PBut-b-PEO vesicles was studied by confocal microscopy. This osmotic imbalance was created by performing the photo-induced polymerization of acrylamide inside these giant polymersomes, mimicking cell-like confinement. Experimental conditions (irradiation time, relative concentration of monomer and photo-initiator) were optimized to induce the fastest and highest osmotic pressure difference in bulk solution. When confined inside polymersomes with low permeability membrane made of PBut-b-PEO copolymers, this hyperosmotic shock induced a fast disruption of the membrane and polymersome burst. These findings, complementary to hypo-osmotic shock approaches previously reported, are demonstrating the versatility and relevance of controlling and modulating osmotic pressure imbalance in self-assembled artificial cell systems and protocells.

INTRODUCTION

Polymersomes are vesicles formed by the self-assembly of amphiphilic copolymers. Since they were first reported by Meijer [START_REF] Van Hest | Polystyrene-Dendrimer Amphiphilic Block Copolymers with a Generation-Dependent Aggregation[END_REF] and Eisenberg 2 in 1995, extensive research has been carried out, and they have found applications as nanoreactors [START_REF] Kim | A Polymersome Nanoreactor with Controllable Permeability Induced by Stimuli-Responsive Block Copolymers[END_REF] and cell mimics [START_REF] Marguet | Multicompartmentalized polymeric systems: towards biomimetic cellular structure and function[END_REF] as well as in encapsulation technologies and drug delivery. [START_REF] Meng | Stimuli-Responsive Polymersomes for Programmed Drug Delivery[END_REF][START_REF] Discher | Emerging applications of polymersomes in delivery: From molecular dynamics to shrinkage of tumors[END_REF] Because of their inherent structure that makes them able to carry cargoes, control over the release of encapsulated compounds is of primordial importance.

A plethora of stimuli-responsive polymersomes have been developed to satisfy the need for controlled release. [START_REF] Meng | Stimuli-Responsive Polymersomes for Programmed Drug Delivery[END_REF][START_REF] Onaca | Stimuli-Responsive Polymersomes as Nanocarriers for Drug and Gene Delivery[END_REF][START_REF] Discher | Polymersomes[END_REF][START_REF] Li | Stimuli-responsive polymer vesicles[END_REF][START_REF] Hu | Stimuli-Responsive Polymersomes for Biomedical Applications[END_REF][START_REF] Liu | Self-Immolative Polymersomes for High-Efficiency Triggered Release and Programmed Enzymatic Reactions[END_REF][START_REF] Deng | Engineering Intracellular Delivery Nanocarriers and Nanoreactors from Oxidation-Responsive Polymersomes via Synchronized Bilayer Cross-Linking and Permeabilizing Inside Live Cells[END_REF] The variety of potential stimuli can be divided into two main categories: the chemical/biological stimuli (e.g. pH, redox, enzymatic activity) and the physical stimuli (e.g. temperature, ultrasound, light). The controled release of the vesicular content may then have two main causes: i) a direct degradation or increased permeability of the membrane, or ii) an indirect membrane loss of integrity (collapse or bursting) as a consequence of an osmotic imbalance between the lumen of the vesicle and the outer medium which is generated by the stimulus. [START_REF] Li | Stimuli-responsive polymer vesicles[END_REF] In cells, aquaporin channels, caveolar invaginations and the exo/endocytosis machinery are at play to accommodate cell swelling or deswelling. [START_REF] Lang | Functional Significance of Cell Volume Regulatory Mechanisms[END_REF][START_REF] Morris | Cell Surface Area Regulation and Membrane Tension[END_REF] In lipid or polymer vesicles lacking such regulatory mechanisms, acute osmotic imbalance usually leads to membrane permeabilization.

Upon hypo-osmotic shock, vesicles swell and burst, while hypertonic shock leads to vesicle shrinkage or ultimately to irreversible collapse. [START_REF] Salva | Polymersome Shape Transformation at the Nanoscale[END_REF][START_REF] Li | Elasticity of synthetic phospholipid vesicles and submitochondrial particles during osmotic swelling[END_REF][START_REF] Carlsen | Block Copolymer Vesicle Permeability Measured by Osmotic Swelling and Shrinking[END_REF][START_REF] Peyret | Polymersome Popping by Light-Induced Osmotic Shock under Temporal, Spatial, and Spectral Control[END_REF][START_REF] Ménager | Reversible Shrinkage of Giant Magnetoliposomes under an Osmotic Stress[END_REF][START_REF] Claessens | Osmotic shrinkage and reswelling of giant vesicles composed of dioleoylphosphatidylglycerol and cholesterol[END_REF][START_REF] Bernard | Raspberry vesicles[END_REF][START_REF] Pencer | Osmotically Induced Shape Changes of Large Unilamellar Vesicles Measured by Dynamic Light Scattering[END_REF] In particular, light can be used with vesicles containing dyes that may undergo photo-cleavage, and thus increase the internal osmotic pressure. In previous work, we showed that polymersome rupture could be triggered under irradiation with a spectral control, depending on the chemical nature of photo-cleavable molecules and the wavelength of the excitation light. [START_REF] Peyret | Polymersome Popping by Light-Induced Osmotic Shock under Temporal, Spatial, and Spectral Control[END_REF] The present study aims at describing the opposite scenario, and elucidate the effect of a light-induced hypertonic shock on the morphology and fate of polymersomes. A key challenge was to design a chemical process that allowed fast osmotic change under microscope irradiation.

As depicted in Figure 1, an experiment was designed where acrylamide and a hydrophilic radical photo-initiator are co-encapsulated inside the lumen of giant poly(butadiene)-b-poly(ethylene oxide) (PBut-b-PEO) vesicles. Upon UV irradiation, poly(acrylamide) is produced in the vesicles interior. As polymerization progresses, acrylamide monomers are consumed, thus leading to a decrease of the internal osmotic pressure concomitantly with an increase of viscosity. [START_REF] Delzenne | Photopolymerization of acrylamide. I. Formation of the initiating redox system[END_REF][START_REF] Seabrook | Photo-initiated polymerization of acrylamide in water[END_REF][START_REF] Villegas | Aqueous photopolymerization with visible-light photoinitiators: Acrylamide polymerization photoinitiated with a phenoxazine dye/amine system[END_REF] Our working hypothesis is that the osmotic pressure resulting from the photo-polymerization reaction could be reduced at such a rate that weakly permeable polymersome membranes inhibit fast equilibration and induce irreversible membrane collapse and release of the vesicular content.

Methods

Electronic absorption experiments were carried out on a Varian Cary 5000 UV-vis-NIR spectrophotometer. Osmolarity measurements were performed with a freezing point automatic osmometer (Type-15M, Löser, Berlin, Germany). Irradiation experiments were carried out with a Mercury-Xenon 200 W lamp. A filter was used to cut UV light below 300 nm and over 480 nm.

Samples (≈1-2 mL) were placed 1 cm from the light guide output end and irradiated in the dark for a defined time. Osmolarities and viscosities were measured before and after irradiation.

Vesicle preparation

Poly(butadiene)-b-poly(ethylene oxide) (PBut 2.5 -b-PEO 1.3 ) giant polymersomes were prepared from the previously discussed emulsion-centrifugation method. [START_REF] Pautot | Production of Unilamellar Vesicles Using an Inverted Emulsion[END_REF][START_REF] Marguet | Polymersomes in "Gelly" Polymersomes: Toward Structural Cell Mimicry[END_REF][START_REF] Marguet | Polymersomes in Polymersomes: Multiple Loading and Permeability Control[END_REF] This method is rather simple and allows for the preparation of complex and eventually compartmentalized polymersomes with accurate control of the content and good reproducibility. [START_REF] Marguet | Polymersomes in "Gelly" Polymersomes: Toward Structural Cell Mimicry[END_REF][START_REF] Marguet | Polymersomes in Polymersomes: Multiple Loading and Permeability Control[END_REF] Nevertheless, the formed vesicles present some dispersity. The use of a double emulsion approach in microfluidic may overcome this issue if needed but presents some limitations in terms of solvent removal. [START_REF] Shum | Dewetting-Induced Membrane Formation by Adhesion of Amphiphile-Laden Interfaces[END_REF][START_REF] Do Nascimento | Microfluidic Fabrication of Pluronic Vesicles with Controlled Permeability[END_REF][START_REF] Hayward | Dewetting Instability during the Formation of Polymersomes from Block-Copolymer-Stabilized Double Emulsions[END_REF][START_REF] Perro | Mastering a Double Emulsion in a Simple Co-Flow Microfluidic to Generate Complex Polymersomes[END_REF] Briefly, 5 µL of sucrose 0.38 M was poured into 3 mg/mL PBut 2.5 -b-PEO 1.3 in 500 µL toluene. The solution was vigorously hand-shaken for 30 seconds to create a water-in-oil emulsion. An interface was prepared by pouring 30 µL of PBut 2.5 -b-PEO 1.3 (3 mg/mL) in toluene over 30 µL glucose 0.38 M and allowed to stabilize for 30 minutes. 60 µL of the above emulsion was slowly poured over the interface and the sample was immediately centrifuged (3 min, 500 g, ambient temperature). The resulting polymersomes were recovered in the lower phase. In the case of acrylamide and Irgacure-loaded polymersomes, the monomer and initiator were dissolved in a sucrose solution to reach the desired concentration and 5 µL of this solution was used to form the emulsion. The concentration of glucose was adjusted to the same osmotic pressure as the sucrose solution.

Samples were kept in the dark prior to irradiation.

RESULTS AND DISCUSSION

By contrast with the developed strategy that aims at generating an hypo-osmotic shock inside vesicles by exploiting the cleavage of photo-sensitive species enclosed in the vesicle lumen, [START_REF] Peyret | Polymersome Popping by Light-Induced Osmotic Shock under Temporal, Spatial, and Spectral Control[END_REF] we investigated the impact of a fast decrease of the osmotic pressure inside the lumen of giant PBut-b-PEO vesicles. Since osmotic pressure is directly related to the number of molecules at a defined time and in a given volume, polymerization reactions appear to be ideal candidates since the formation of one polymer chain depletes the reservoir from monomers. More specifically, polymerization of acrylamide was chosen as a model reaction (Figure 1). Indeed, poly(acrylamide) is obtained from the polymerization of an acrylamide monomer, which is soluble in water at room temperature and possesses a high constant of propagation (k p ) in water. [START_REF] Seabrook | Photo-initiated polymerization of acrylamide in water[END_REF] 2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure, Figure 2A) was chosen as a photo-initiator because it is fairly soluble in water and has proven to be effective in photoinitiated polymerization reactions. [START_REF] Fairbanks | Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2,4,6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility[END_REF] The absorbance spectra for different Irgacure concentrations were monitored with a spectrophotometer to verify that the initiator could be activated in the wavelength range of a mercury-xenon 200 W UV lamp (300-480 nm) (Figure 2B). While 0.10 and 0.25 wt/v (%) Irgacure only show low signal in this range of wavelengths, a significant increase in absorbance is observed for 0.5 wt/v (%) Irgacure. In photo-polymerization processes, both monomer and initiator concentration have an impact on the rate of the reaction. [START_REF] Andrzejewska | Photopolymerization kinetics of multifunctional monomers[END_REF] Therefore, the photo-polymerization was first performed in bulk solution using different monomer-to-initiator ratio to verify the effective polymerization of acrylamide under these conditions and to monitor the changes in viscosity and osmolarity. In each experiment, the monomer and initiator were mixed in a 0. The large peaks indicate the high polydispersity of the samples, as typically observed for free radical polymerization reactions. However, a net shift between the peaks indicates the influence of the concentration of the monomer on the final molar masses of the polymers. Indeed, higher molar masses are obtained with higher monomer concentrations, also suggesting higher changes in osmolarity and viscosity. To test this hypothesis, osmolarity and viscosity measurements were performed before and after irradiation of the samples (Figure 3). As expected, a decrease in osmolarity (Figure 3A) and an increase in viscosity (Figure 3B) were observed for all monomerto-initiator ratios with the most prominent differences obtained for 0.5 wt/v (%) Irgacure concentration. In the absence of initiator, no changes in either osmolarity or viscosity were observed, showing that polymerization cannot occur in the absence of Irgacure as a source of radicals. Kinetic measurements were also performed to confirm the fact that the polymerization, hence the change in osmolarity, was occurring quickly. Figure 3C shows the evolution of the osmolarity and the normalized osmolarity difference ΔOsm with time when irradiating a mixture containing 20 g/L acrylamide and 0.5 wt/v (%) Irgacure in 0.3 M sucrose. Figure 3D displays the corresponding monomer conversion (details on the determination of conversion using NMR and osmolarity can be found in supporting information). We observed that osmolarity decreased by 20 % after only 30 s, and 30 % after 60 s, which corresponds to 45 ± 5 % monomer conversion, and 64 ± 4 % monomer conversion, respectively.

Having determined the optimal concentration conditions to induce the highest osmotic shock in a rapid way, the photo-initiated reaction was then triggered inside the lumen of the giant PBut-b-PEO polymersomes as schematically represented in Figure 1. Different ratios of monomer and initiator solubilized in sucrose were loaded in giant PBut-b-PEO vesicles using an emulsioncentrifugation protocol initially developed by Pautot et al. [START_REF] Pautot | Production of Unilamellar Vesicles Using an Inverted Emulsion[END_REF] and further adapted. [START_REF] Marguet | Polymersomes in "Gelly" Polymersomes: Toward Structural Cell Mimicry[END_REF] Vesicles containing 0.1 wt/v (%) Irgacure did not show any change, even after 10 min irradiation at maximum lamp intensity, suggesting that the build-up in osmotic pressure is too small and too slow in these conditions (see supporting information). However, the outcome was drastically different for vesicles loaded with either 0.25 or 0.50 wt/v (%) initiator with respectively 40 and 20 g/L monomer. We observed rapid vesicle rupture (within less than 1-minute UV irradiation) for most vesicles. Figure 4B and 4C are snapshots of vesicles during the irradiation sequence.

Controls were performed to verify that no explosion occurred in empty (sucrose-loaded) vesicles under the same conditions, confirming that the observed bursting was not due to any possible heating effect during UV irradiation.

Remarkably, the membrane rim seems to curl towards the inner medium, where the viscosity is higher, in agreement with previous studies reporting polymersome bursting. [START_REF] Peyret | Polymersome Popping by Light-Induced Osmotic Shock under Temporal, Spatial, and Spectral Control[END_REF][START_REF] Mabrouk | Bursting of sensitive polymersomes induced by curling[END_REF] Altogether, these results confirm our hypothesis that the low membrane permeability of polymer vesicles drastically restricts effective water diffusion and therefore prevents a re-equilibration of the osmotic pressure difference between both sides. More generally, these results evidenced the importance of controlling osmotic pressure variations in the context of cell membrane mimics.

Subtle equilibrium of forces, surface-area-volume ratio, swelling, pore formation, mechanical tension and their dynamics are leading to intriguing phenomena from popping to membrane deformation and quasi-homeostatic self-regulatory behavior. [START_REF] Peyret | Polymersome Popping by Light-Induced Osmotic Shock under Temporal, Spatial, and Spectral Control[END_REF][START_REF] Ho | Mixing Water, Transducing Energy, and Shaping Membranes: Autonomously Self-Regulating Giant Vesicles[END_REF][START_REF] Su | Pulsatile Gating of Giant Vesicles Containing Macromolecular Crowding Agents Induced by Colligative Nonideality[END_REF][START_REF] Oglęcka | Oscillatory phase separation in giant lipid vesicles induced by transmembrane osmotic differentials[END_REF] CONCLUSIONS While a classical approach to cause membrane rupture of a vesicle is to produce a hypo-osmotic shock, which swells the vesicle and increase its membrane tension, the effect of a hyper-osmotic shock is less intuitive and has been overlooked. In the present work, we have investigated the impact of light-induced hypertonic shocks on giant polymer vesicles. Light was used as an external trigger to induce a fast polymerization reaction inside the lumen of the vesicles. Here, we demonstrate that, under optimal conditions, this reaction generates a fast decrease of the internal osmotic pressure and leads to vesicle rupture due to the low water diffusion conferred by the weakly permeable membrane. This mechanism offers a new route to control directed delivery in nanomedicine. Instead of producing low small molecular fragments during the hypo-osmotic shock that can eventually create ROS that may be harmful for neighboring cells, the release of polymer chains together with the active species may be envisioned as a more gentle and harmless strategy. In addition, the approach can be extended to any other monomers, included charged ones, if the polymerization process is fast and the obtained polymers do not interact with the polymersome membrane. After demonstrating the feasibility of the approach, future works should be dedicated to reach a proof of concept within the context of a relevant nanomedical application and in contact with cells.

ASSOCIATED CONTENT Supporting Information. Details on the calculation of monomer conversion, SEC traces of obtained polymer and additional confocal images are provided in supporting information.

Table of Content Graphic

Figure 1 .

 1 Figure 1. Schematical representation of UV photo-induced polymerization of acylamide inside

  Viscosities were determined with a density meter (DMA generation M from Anton Paar) equipped with a rolling ball micro-viscometer (Lovis 2000 M/ME from Anton Paar) at 20°C. Laser scanning confocal microscopy images were acquired on an inverted Leica TCS SP5 microscope equipped with an HCX PL APO 63×, NA 1.4 oil immersion objective in transmission mode. Samples (≈20 μL) were injected in a homemade chamber that was sealed to prevent evaporation. The light guide output end of the UV lamp was placed 1 cm away from the chamber for optimized irradiation. Images were collected in simultaneous mode using a resonant scanner at 8000 Hz in bidirectional mode and processed with the ImageJ freeware. Size exclusion chromatography in water was performed on a Wyatt apparatus. Samples (≈1 mL) were prepared from the dissolution of 5 mg lyophilised polymer in a 0.1 M NaNO 3 + 0.1 M H 2 O 4 P buffer and were filtered (0.45 µm) before injection.[START_REF] Van Hest | Polystyrene-Dendrimer Amphiphilic Block Copolymers with a Generation-Dependent Aggregation[END_REF] H NMR experiments were performed in D 2 O at 25 °C on a Bruker Advance 400 spectrometer operating at 400 MHz calibrated to the solvent peak.

Figure 2 .

 2 Figure 2. A) Chemical structure of Irgacure photo-initiator; B) Absorbance spectra of Irgacure

  3 M sucrose solution (used for polymersome formation) and irradiated 5 minutes with a mercury-xenon 200 W lamp between 300 and 480 nm. Figures 2C, 2D and 2E show the chromatograms obtained for the size exclusion chromatography in water of the poly(acrylamides) generated after photo-polymerization with different concentrations of monomer and initiator.

Figure 3 .

 3 Figure 3. A) Osmolarity and B) viscosity measurements on obtained poly(acrylamides) for

  The light guide output end of the mercury-xenon 200 W UV lamp was placed over the hermetic chamber containing the polymersomes on the stage of a confocal microscope as shown in Figure 4A. The behavior of vesicles could thus be monitored by confocal microscopy under white light observation during irradiation.

Figure 4 .

 4 Figure 4. A) Confocal setup. The light guide output end of a mercury-xenon UV lamp is placed

ACKNOWLEDGMENT SCL and PN thank the University of Bordeaux Foundation through the Chair "Chemistry and Self-Assembly" for financial support. SL thanks the Agence Nationale de la Recherche (ANR program NO-SynthCell N°ANR-14-CE16-0015). The CPER CampusB project funded by the French state and the Region Nouvelle Aquitaine is also acknowledged. Dr. Hang Zhao is kindly acknowledged for graphical support.

AUTHOR INFORMATION

Corresponding Authors

Pierre Nassoy (pierre.nassoy@u-bordeaux.fr) Sébastien Lecommandoux (lecommandoux@enscbp.fr)

Determination of monomer conversion

Osmolarity method

The measured osmolarity (Osm) is the addition of contributions from concentrations in sucrose,

NMR method

As shown in Figure S1, monomer conversion was also determined more precisely by comparing the integrations of the vinyl protons corresponding to the remaining monomer with the integration of polymer backbone signals.

Figure S1: Determination of monomer conversion by 1 H NMR.

Table S1 provides all kinetic data and shows the comparison between the two methods.

Table S1: Kinetic measurements of the polymerization of acrylamide at 20 g/L, using 0.5 % wt/v Irgacure, under UV irradiation (300 -480 nm) with a mercury-xenon 200 W lamp in 0.3 M sucrose.

SEC traces of obtained polymers

Confocal images


Sébastien Lecommandoux

Harm-Anton Klok

Zhiyuan Zhong

Timothy J Deming

Anton Klok

Stefan ; Oelmann

Alessandra ; Travanut

Dennis ; Barther

Manuel ; Romero

Steven ; Howdle

Cameron ; Alexander

Michael Meier

Annelies ; Wauters

Imke ; Pijpers

Alexander ; Mason

David ; Williams

Jurjen ; Tel

Huanli ; Sun

Zhiyuan Zhong

; Gangapurwala

Gauri ; Pretzel

David ; Leiske

Meike ; Wang

; Hoeppener

Stephanie ; Schubert

Stephanie ; Brendel

Johannes ; Schubert

Claudia ; Battistella

Romain ; Guiet

Olivier ; Burri

Arne ; Seitz

Stephane ; Escrig

Graham ; Knott

Anders ; Meibom

Jonathan ; Cressonnier

Catherine ; Lefay

Didier ; Gigmes

Yohann ; Guillaneuf

Julien Nicolas

Thorsten ; Lückerath

Tina ; Strauch

Kaloian ; Koynov

Christopher ; Barner-Kowollik

David ; Ng

Tanja Weil

Le Fer

Gaëlle ; Wirotius

Anne-Laure ; Brûlet

Annie ; Garanger

Elisabeth ; Lecommandoux

Guojun ; Xie

Michael R ; Martinez

Mateusz; Sheiko Sergei ; Olszewski

Matyjaszewski

Krzysztof

Olga ; Verbraeken

Bart ; Hoogenboom

Damla ; Mergel

Olga ; Van Der Mei

Henny ; Busscher

Henk ; Van Rijn

Christopher ; Garvey

Hongxu ; Lu

Martina Stenzel

Caroline ; Bray

Pratik ; Gurnani

Edward ; Mansfield

Raoul ; Peltier

Sebastien Perrier

Future directions at the frontier of polymer science and biology

come   L'archive ouverte pluridisciplinaire

interest to the readership of Biomacromolecules, including biomaterials design, renewable materials, polymer micelles and vesicles, nanoparticles, hydrogels and nanogels for nanomedicine, green approaches for polymer design, biobased nanocomposites, biosourced amphiphiles, biocompatible and functional emulsions, macromolecular engineering for biomaterial design, DNA-and protein-based bioconjugates, design of polymer interface for controlled interaction with living organisms, bioadhesives, antimicrobial polymers and surfaces. Altogether, these contributions are providing a brilliant overview of the current state-of-the-art in the field and are highlighting exciting future emerging challenges and opportunities at the frontier of polymer science and life science, in a broad manner.

A first set of manuscripts focuses on the elaboration of bio-based and renewable materials and biomaterials. Sylvain Caillol et al. 4 give a comprehensive overview on the recent advances about the synthetic pathways reported to provide suitable monomers from fatty acids and their derivatives for radical polymerization together with the different application of the resulting bio-based polymeric materials. Karen Wooley et al. [START_REF] Wacker | Harnessing the Chemical Diversity of the Natural Product Magnolol for the Synthesis of Renewable, Degradable Neolignan Thermosets with Tunable Thermomechanical Characteristics and Antioxidant Activity[END_REF] highlight the chemical diversity of the natural product magnolol for the synthesis of renewable, degradable neolignan thermosets with tunable thermomechanical characteristics and antioxidant activity.

The group of K. Masami 6 presents a series of cinnamic monomers, which can be derived from naturally occurring phenylpropanoids that were radically copolymerized by NMP or RAFT with vinyl monomers. The solution properties of the resulting copolymers were studied. Interestingly, H. Cramail et al. 7 present the synthesis and self-assembly of Xylan-based amphiphiles. Xylan oligomers were conjugated to lipid derivatives by click chemistry and the resulting amphiphiles were self-assembled using microfluidic approach into vesicles that can be use to load antifungal molecules. In another example, Z. Li et al. 8 Ng and T. Weil 18 described a convenient, light-mediated approach toward DNA-polymer conjugates via the grafting-from approach. S. Lecommandoux et al. 19 presented the synthesis and original thermoresponsive behavior of hybrid diblock copolypeptides composed of synthetic poly(L-glutamic acid) and recombinant elastin-like polypeptides.

The surface and interfacial properties of polymers and nanoparticles with biology was also illustrated in this special issue. In this context, K. Matyjaszewski et al. 20 first proposed an extensive review on molecular bottlebrushes as building blocks for the design of unique polymeric materials whose physical and biological properties are fundamentally governed by their densely grafted structures. D. Mecerreyes et al. 21 presented an interesting overview of the emerging strategies developed to manufacture 3D conductive scaffolds, the techniques used to fully characterize them, and the biomedical fields where they have been applied to.

Corresponding Authors

*E-mail: lecommandoux@enscbp.fr *E-mail: harm-anton.klok@epfl.ch *E-mail: zyzhong@suda.edu.cn *E-mail: demingt@seas.ucla.edu

  evidenced the preparation of amphiphilic poly(ethylene glycol)-b-poly(γ-butyrolactone) diblock copolymer via ring opening polymerization catalyzed by a cyclic trimeric phosphazene base or alkali alkoxide. The catalytic/initiating organic systems showed moderate control on the ring opening polymerization of of γ-butyrolactone (γBL) and successfully produced PEG-b-PγBL diblock copolymers with varied molecular weights and relatively narrow molecular weight distributions. In another study, S. Anastasiadis et al. 9 studied the structure and dynamics of two bio-based polyester polyols in the bulk and close to surfaces in polymer / layered silicate nanocomposites. Another series of manuscript are illustrating the interest and impact of polymers in the field of biology, biomedicine and nanomedicine. In a first paper the groups of A. Alexander and M. Meier 10 present the synthesis of amphiphilic star-shaped block copolymers containing thioether groups, which could be oxidized to sulfones in order to further tune the polarity of the polymer chains, via the Passerini reaction. The resulting amphiphilic copolymers were demonstrated to act as unimolecular micellar encapsulants that can be used as a promising nanomedicine. In another paper, J. van Hest et al. 11 demonstrated the generation of welldefined nanotubes based on polymersomes. The resulting nanotubes were extensively characterized and successfully loaded with model drugs, providing a promising platform for implementation in biomedical applications in which discrete structure and functionality are essential features. Z. Zhong et al. 12 reported that smart polymersomes based on PEG-bpoly(trimethylene carbonate-co-dithiolane trimethylene carbonate) dually functionalized with cRGD and fusogenic GALA peptides enable α ν β 3 -specific and high-efficiency cytosolic delivery of cytochrome C, highlighting the therapeutic interest of such a strategy. U. Schubert et al. 13 reported the synthesis of pH-sensitive nanogels, which are based on the monomer N-[(2,2-dimethyl-1,3-dioxolane)methyl]acrylamide (DMDOMA) bearing an acid cleavable acetal group. In vitro studies revealed a good compatibility of the unloaded nanogel and the capability of the doxorubicin loaded nanogel to mediate cytotoxic effects in a concentration and time-dependent manner with an even higher efficiency than the free drug. D. Gigmes and T. Trimaille 14 developed interesting an injectable and biodegradable hydrogel based on an amphiphilic PNIPAAm-b-PLA-b-PEG-b-PLA-b-PNIPAAm pentablock copolymer synthesized by ring-opening polymerization/nitroxide-mediated polymerization (ROP/NMP) combination. The hydrogel was shown to be cytocompatible (neuronal cells, in vitro) and injectable, displaying highly attractive features for use in brain/soft tissue engineering as well as in drug delivery. H.-A. Klok et al. 15 presented a first proof-of-concept that demonstrates the feasibility of NanoSIMS to monitor the intracellular localization of polymer conjugates using poly(N-(2-hydroxypropyl) methacrylamide)) as a prototypical polymer-drug conjugate. J. Nicolas et al. 16 evidenced the successful copolymerization of 2-methylene-1,3-dioxepane (MDO) and different vinyl ether (VE) monomers by free-radical radical ring-opening copolymerization. The different copolymers were formulated into nanoparticles. Their stability, hydrolytic and enzymatic degradability and cell viability were evaluated, demonstrating the interest of these original polymer structures. Another series of papers are dealing with proteins, DNA and bioconjugates. The group of R. Mezzenga 17 first reviewed the current knowledge regarding the conformational flexibility of fibronectin, with an emphasis on how it regulates the ability of fibronectin to interact with various signaling molecules and cell-surface receptors and to form supramolecular assemblies and fibrillar structures. In a nice collaborative contribution, K. Barner-Kowollik, D.

K

  . Glinel and A. Jonas 22 demonstrated entrapment of the commensal skin bacteria Staphylococcus epidermidis in mats composed of soft nanotubes made by membranetemplated layer-by-layer assembly These patches offer a promising methodology for the fabrication of bacterial skin dressings for the treatment of skin dysbiosis while preventing adverse effects due to bacterial proliferation. B. Schmidt and M. Antonietti 23 proposed waterin-water Pickering emulsion stabilized by polydopamine particles that was further crosslinked via poly(acrylic acid) and carbodiimide, resulting in strengthening the stability of emulsion droplets in a colloidosome-like structure. R. Hoogenboom et al. 24 described a new method for the synthesis of superhydrophilic poly(2-alkyl-2-oxazoline)s from poly(2-ethyl-2oxazoline). P. van Rijn et al. 25 demonstrated that poly-N-isopropylmethacrylamide based microgel coatings prepared via a spraying approach could advantageously prevent bacterial adhesion. In other interesting studies, S. Mecking et al. 26 developed multivalent carbohydrate-functionalized polyethylene nanocrystals and M. Stenzel et al. 27 evidenced that the architecture of the hydrophilic glycopolymer brush on the surface of polymeric micelles affects the interaction with cancer cells. Finally, S. Perrier et al. 28 explored the structureactivity relationship of synthetic homopolymers and copolymers of sodium 2-acrylamido-2methylpropane sulfonate, with a focus on the effect of molecular weight, co-monomer type, charge dispersion and polymer architecture on protein stabilization. This Special Issue provides a sense of up-to-date research and development of polymers at the interface with biology, with the most recent trends in the field. We are looking forward to how these exciting results that were presented during BPC 2018 develop and expand into new areas. A following-up edition of Bordeaux Polymer Conference is already expected in 2022 (BPC 2022).

ORCID

Sébastien Lecommandoux: 0000-0003-0465-8603 Harm-Anton Klok: 0000-0003-3365-6543 Zhiyuan Zhong: 0000-0003-4175-4741 Timothy J. Deming: 0000-0002-0594-5025