Philippe Guégan's research while affiliated with Sorbonne Université and other places

Three different amphiphilic block copolymer families were synthesized to investigate new opportunities to enhance gene delivery via Hydrodynamic Limb Vein (HLV) injections. First a polyoxazoline‐based family containing mostly one poly(2‐methyl‐2‐oxazoline) (PMeOx) block and a second block POx with an ethyl (EtOx), isopropyl (iPrOx) or phenyl substituent (PhOx) has been synthesized. Then an ABC poly(2‐ethyl‐2‐oxazoline)‐ b ‐poly(2‐n‐propyl‐2‐oxazoline)‐ b‐ poly(2‐methyl‐2‐oxazoline) triblock copolymer was synthesized, with a thermosensitive middle block. Finally, polyglycidol‐ b ‐polybutylenoxide‐ b ‐polyglycidol copolymers with various molar masses and amphiphilic balance were produced. The simple architecture of neutral amphiphilic triblock copolymer is not sufficient to obtain enhanced in vivo gene transfection. Double or triple amphiphilic neutral block copolymers are improving the in vivo transfection performances through HLV administration as far as a block having an LCST is incorporated in the vector. The molar mass of the copolymer does not seem to affect the vector performances in a significant manner. This article is protected by copyright. All rights reserved

The anionic ring‐opening copolymerization of commercially available bio‐based cardanol glycidyl ether (CGE) was investigated without any prior purification. As a first step, anionic‐ring‐opening homopolymerization was attempted through active chain‐end and monomer‐activated mechanisms. Both strategies were unsuccessful. Conversely, in a second step, the anionic alternating ring‐opening copolymerization (AAROP) of CGE with the renewable N ‐acetyl homocysteine thiolactone (NHTL) was successfully carried out in the presence of a strong base. Anisole, a solvent classified as sustainable and rarely used in anionic ring‐opening polymerization, proved to be a suitable for the AAROP. This polymerization is an unusual example of synthesis of linear polyesters with cardanol‐based monomers. The copolymers were carefully characterized by ¹ H, ¹³ C, COSY, HSQC, ¹ H‐ ¹⁵ N NMR and MALDI‐ToF, demonstrating an alternating structure. Then, CGE was copolymerized with NHTL and another additional epoxide. The cardanol‐derived monomers enable the preparation of functionalizable poly(ester‐ alt ‐thioether) bearing multiple allyl and alkene groups. The AAROP method in anisole offers new opportunity for green anionic polymerization through the use of sustainable chemicals, witnessed by the valorization of cardanol‐derived compounds and expands the scope of synthesized renewable polyesters.

The chemical recyclability of poly(ester-alt-thioether) structures is investigated. Different polymers were synthesized by alternating anionic ring-opening copolymerization of thiolactone and epoxide monomers using benzyl alcohol – BEMP phosphazene base as initiating system. Controlled structures with number-average molar masses between 2000 and 5000 g mol⁻¹ were obtained. In a second time, degradation studies were carried out by methanolysis in acidic and basic conditions. The influences of the base/acid concentration and of the epoxide unit lateral substituent on the degradation rate were also investigated. The structure of degradation product has been confirmed by ¹H, ¹³C NMR, SEC and ESI mass spectrometry, and corresponds to α-hydroxy-ω-methyl ester repeating unit molecules. These molecules were subsequently used as A–B monomers in step-growth polymerization syntheses using either p-toluene sulfonic acid (PTSA) or titaniumbutoxide (Ti(OBu)4) as catalyst. The resulting condensation polymers were analyzed by NMR, SEC, MALDI ToF, TGA and DSC. Identical structures, comparable molar masses and slightly higher glass transition temperatures have been obtained compared to the ones of the native polymers synthesized by AROP.

Mimicking and extending the gating properties of biological pores is of paramount interest for the fabrication of membranes that could be used in filtration or drug processing. Here, we build a selective and switchable nanopore for macromolecular cargo transport. Our approach exploits polymer graftings within artificial nanopores to control the translocation of biomolecules. To measure transport at the scale of individual biomolecules, we use fluorescence microscopy with a zero-mode waveguide set up. We show that grafting polymers that exhibit a lower critical solution temperature creates a toggle switch between an open and closed state of the nanopore depending on the temperature. We demonstrate tight control over the transport of DNA and viral capsids with a sharp transition (∼1 °C) and present a simple physical model that predicts key features of this transition. Our approach provides the potential for controllable and responsive nanopores in a range of applications.

For the first time, the ring-opening copolymerization of γ-thiobutyrolactone and ethylene carbonate was investigated using benzyl alcohol–phosphazene bases as initiating systems. Full conversions of both monomers were obtained when the...

Gene delivery is now a part of our therapeutic arsenal for vaccination and treatments of inherited or acquired diseases. Polymers represent an opportunity to develop new synthetic vectors for gene transfer, with a prerequisite of improved delivery and reduced toxicity compared to existing polymers. Here, we report the synthesis in a two‐step's procedure of linear poly(ethylenimine‐b‐2‐isopropyl‐2‐oxazoline) block copolymers with the linear polyethylenimine (lPEI) block of various molar masses; the molar mass of the poly(2‐isopropyl‐2‐oxazoline) (PiPrOx) block been set to 7 kg.mol−1. Plasmid DNA condensation is successfully achieved, and in vitro transfection efficiency of the copolymers is at least comparable to that obtained with the lPEI of same molar mass. lPEI‐b‐PiPrOx block copolymers are however less cytotoxic than their linear counterparts. PiPrOx could be a good alternative to PEG which is often used in drug delivery systems. The grafting of histidine moieties on the lPEI block of lPEI‐b‐PiPrOx does not provide any real improvement of the transfection efficiency. A weak DNA condensation is observed, due to increased steric hindrance along the lPEI backbone. The low cytotoxicity of lPEI‐b‐PiPrOx makes of this family a good candidate for future gene delivery developments. This article is protected by copyright. All rights reserved

For polymersome-based nanoreactor purposes, we herein present the synthesis and characterization of well-defined star amphiphilic copolymers composed of a beta-cyclodextrin (βCD) core and seven poly(butylene oxide)-block-polyglycidol (PBO-PGL) arms per side (βCD-(PBO-PGL)14). The self-assembly behavior of 14-armed βCD-(PBO-PGL)14 and PGL-PBO-PGL (linear analogues without the βCD segment) was investigated using scattering techniques for comparison. The morphologies, including vesicles and micelles, are governed by the hydrophobic-to-hydrophilic (weight) ratio, regardless of the polymer architecture (linear or star). Interestingly, despite notable differences in polymer conformation, the produced supramolecular structures were evidenced to be fairly similar on the structural point of view. We subsequently investigated the ion permeability of the membranes of the self-assemblies focusing on the impact of the presence of βCD. The results demonstrated that the βCD-containing vesicular membranes are less permeable to H⁺, compared with βCD-free vesicular membranes. The presence of βCD in planar membranes also influences the K⁺Cl⁻ permeability to some extent. Thus, βCD-containing membranes can be considered as potential candidates in designing nano-containers towards applications where precise changes in environmental pH are required.