Issue 12, 2023

Degradable polyisoprene by radical ring-opening polymerization and application to polymer prodrug nanoparticles

Abstract

Radical ring-opening polymerization (rROP) has received renewed attention to incorporate cleavable linkages into the backbones of vinyl polymers, especially from cyclic ketene acetals (CKAs). Among the monomers that hardly copolymerize with CKAs are (1,3)-dienes such as isoprene (I). This is unfortunate since synthetic polyisoprene (PI) and its derivatives are the materials of choice for many applications, in particular as elastomers in the automotive, sport, footwear, and medical industries, but also in nanomedicine. Thionolactones have been recently proposed as a new class of rROP-compatible monomers for insertion of thioester units in the main chain. Herein, we report the synthesis of degradable PI by rROP via the copolymerization of I and dibenzo[c,e]oxepane-5-thione (DOT). Free-radical polymerization as well as two reversible deactivation radical polymerization techniques were successfully used for the synthesis of (well-defined) P(I-co-DOT) copolymers with adjustable molecular weights and DOT contents (2.7–9.7 mol%). Reactivity ratios of rDOT = 4.29 and rI = 0.14 were determined, suggesting preferential incorporation of DOT in comparison to I. The resulting P(I-co-DOT) copolymers were successfully degraded (from −47% to −84% decrease in Mn) under basic conditions. As a proof of concept, the P(I-co-DOT) copolymers were formulated into stable and narrowly dispersed nanoparticles, showing similar cytocompatibility on J774.A1 and HUVEC cells compared to their PI counterparts. Furthermore, Gem-P(I-co-DOT) prodrug nanoparticles were synthesized by the “drug-initiated” method and exhibited significant cytotoxicity on A549 cancer cells. P(I-co-DOT) and Gem-P(I-co-DOT) nanoparticles were degraded under basic/oxidative conditions by bleach and under physiological conditions in the presence of cysteine or glutathione.

Graphical abstract: Degradable polyisoprene by radical ring-opening polymerization and application to polymer prodrug nanoparticles

Supplementary files

Article information

Article type
Edge Article
Submitted
23 9 2022
Accepted
20 2 2023
First published
06 3 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 3311-3325

Degradable polyisoprene by radical ring-opening polymerization and application to polymer prodrug nanoparticles

M. Lages, T. Pesenti, C. Zhu, D. Le, J. Mougin, Y. Guillaneuf and J. Nicolas, Chem. Sci., 2023, 14, 3311 DOI: 10.1039/D2SC05316K

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