Vinyl polymer engineering for the development of new materials for biomedical applications Julien Nicolas Université Paris-Saclay, CNRS, France Synthetic polyesters and polypeptides are regarded as gold standards for the development of polymer-based nanoscale systems (e.g., polymer nanoparticles, polymer prodrugs) for biomedical applications. However, despite their non-degradability, vinyl polymers offer many advantages in terms of macromolecular engineering. For instance, owing to their great versatility and ease of functionalization, vinyl polymers can be advantageously used for the design of polymer prodrugs for drug delivery purposes. Our group has recently reported on the design of a new class of polymer prodrug nanocarriers by using the “drug-initiated” method, which consists in the controlled growth of vinyl polymers from anticancer drug-bearing controlling agents for reversible deactivation radical polymerization to prepare well-defined and high drug content polymer prodrug nanoparticles with in vitro and in vivo anticancer activity.1,2,3 This approach has also been applied to the synthesis of water-soluble polymer prodrugs for subcutaneous administration of irritant/vesicant anticancer drugs as an alternative to traditional intravenous chemotherapy.4 To challenge traditional polyesters, a lot of effort is also currently focused on the design of degradable vinyl polymers to make them suitable for biomedical applications.5 One of the most potent approaches relies on the introduction of labile groups in the carbon polymer backbone by radical ring-opening polymerization (rROP) of cyclic monomers (e.g., cyclic ketene acetals) with traditional vinyl monomers.6 Yet, despite promising achievements, important limitations still stand, such as the poor hydrolytic degradation of rROP copolymers in physiological conditions, which still cannot compete that of aliphatic polyesters. In this context, we have recently reported the development of: (i) new copolymerization systems that enable the synthesis of well-defined, thermosensitive vinyl copolymers with enhanced hydrolytic degradation in water and PBS (Figure 1)7 and (ii) new polymerization processes to generate aqueous suspensions of degradable vinyl copolymer nanoparticles for biomedical applications.8
Figure 1. Synthesis of thermosensitive vinyl copolymers obtained by copolymerization of acrylamide (AAm) and cyclic ketene acetals (CKA) that can form nanoparticles and degrade faster than PLA and PLGA. References: 1. 1. Nicolas, J. Chem. Mater. 2016, 28, 1591 2. 2. Guégain, E.; Tran, J.; Deguettes, Q.; Nicolas, J. Chem. Sci. 2018, 9, 8291 3. 3. Lages, M.; Pesenti, T.; Zhu, C.; Le, D.; Mougin, J.; Guillaneuf, Y.; Nicolas, J. Chem. Sci. 2023, 14, 3311 4. 4. Bordat, A.; Boissenot, T.; Ibrahim, N.; Ferrere, M.; Levêque, M.; Potiron, L.; Denis, S.; Garcia-Argote, S.; Carvalho, O.; Abadie, J.; Cailleau, C.; Pieters, G.; Tsapis, N.; Nicolas, J. J. Am. Chem. Soc. 2022, 144, 18844
5. 5. Delplace, V.; Nicolas, J. Nature Chem. 2015, 7, 771 6. 6. Pesenti, T.; Nicolas, J. ACS Macro Letters 2020, 9, 1812 7. 7. Bossion, A.; Zhu, C.; Guerassimoff, L.; Mougin, J.; Nicolas, J. Nature Commun. 2022, 13, 2873 8. 8. Zhu, C.; Denis, S.; Nicolas, J. Chem. Mater. 2022, 34, 1875
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