Novel Biodegradable Polymer with Redox-Triggered Backbone Cleavage Through Sequential 1,6-Elimination and 1,5-Cyclization Reactions

5 years ago

Novel Biodegradable Polymer with Redox-Triggered Backbone Cleavage Through Sequential 1,6-Elimination and 1,5-Cyclization Reactions

Chang-Hee Whang, Seongbong Jo, Ho-Wook Jun, Jun Chen, Jungeun Bae, Kyeong Soo Kim

In the past decade, the self-immolative biodegradable polymer arose as a novel paradigm for its efficient degradation mechanism and vast potential for advanced biomedical applications. This study reports successful synthesis of a novel biodegradable polymer capable of self-immolative backbone cleavage. The monomer is designed by covalent conjugations of both pendant redox-trigger (p-nitrobenzyl alcohol) and self-immolative linker (p-hydroxybenzyl alcohol) to the cyclization spacer (n-2-(hydroxyethyl)ethylene diamine), which serves as the structural backbone. The polymerization of the monomer with hexamethylene diisocyanate yields a linear redox-sensitive polymer that can systemically degrade via sequential 1,6-elimination and 1,5-cyclization reactions within an effective timeframe. Ultimately, the polymer's potential for biomedical application is simulated through in vitro redox-triggered release of paclitaxel from polymeric nanoparticles. A biodegradable polymer capable of reduction-induced spontaneous degradation is synthesized for potential biomedical applications. Integration of pendant p-nitrobenzyl redox trigger along with intramolecular cyclization spacer and self-immolative linker enables a cascade cleavage of polymer upon reduction. Ultimately, the redox-triggered release of chemotherapeutic agent, paclitaxel, is observed from polymeric nanoparticles.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/marc.201700395