Photo-Triggered Release of Caged Camptothecin Prodrugs from Dually Responsive Shell Cross-Linked Micelles

Abstract

We report on the fabrication of dynamic covalent shell cross-linked (SCL) micelles with hydrophobic cores conjugated with photocaged chemotherapeutic drugs and coronas functionalized with ligands for tumor cell targeting. Two types of amphiphilic diblock copolymers, P(CL-g-CPT)-b-P(OEGMA-co-MAEBA)-CPT and PCL-b-P(OEGMA-co-MAEBA-co-FA), were synthesized via the combination of ring-opening copolymerization (ROP) of e-caprolactone (CL) and 2-bromo-e-caprolactone (CL-Br), atom transfer radical polymerization (ATRP) of oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) and p-(methacryloxyethoxy) benzaldehyde (MAEBA) comonomers, and “click” post-functionalization with photocaged camptothecin (CPT) prodrug and alkynyl-functionalized folic acid (FA) moieties, respectively. Mixed micelles coassembled from PCL-b-P(OEGMA-co-MAEBA-co-FA) and P(CL-g-CPT)-b-P(OEGMA-co-MAEBA)-CPT possess hydrophobic cores conjugated with photocaged CPT prodrugs and hydrophilic outer coronas covalently attached with aldehyde gr...