Development of a facile strategy to synthesize PLA-based reduction-responsive shell-sheddable nanoassemblies for drug delivery****

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Current trend in polymer-based nanomedicine for cancer therapy mainly focuses on the development of block copolymer-based nanoassemblies with hydrophobic cores enabling the encapsulation of hydrophobic anticancer drugs. Recently, well-defined block copolymers consisting of hydrophobic polylactide (PLA) and hydrophilic poly(ethylene glycol) (PEG) blocks have been currently practiced in clinics. However, the conventional systems rely on diffusion-controlled mechanism, which is passive, uncontrolled, and slow for the release of encapsulated anticancer drugs. The research opportunity here is to explore reduction-responsive degradation platform for cancer therapy with enhanced/controlled drug release profile. ****In this proposed research, in collaboration with Advanced Polymeric Materials (APM) located in Montreal, we will explore a facile strategy to incorporate disulfide linkage into the design of conventionally-designed PLA-b-PEG block copolymers. The strategy will utilize a combination of click-type alkyne-azido cycloaddition reaction with ring opening polymerization to synthesize novel block copolymer having a reduction-responsive disulfide linkage (SS) at the junction of PLA and PEG blocks, thus PLA-SS-PEG block copolymers. Important parameters including block lengths and the number of alkyl groups adjacent to SS linkage will be varied to understand the structure-property relationship. Further, the synthesized copolymers will be evaluated for effective intracellular drug delivery. This collaborative project will offer APM a great opportunity to be competitive in markets over their competitors.