Redox-responsive phenyl-functionalized polylactide micelles for enhancing Ru complexes delivery and phototherapy

Poly(ethylene glycol)-poly(lactic acid)block copolymer(PEG-PLA)is one of the most widely used biomed-ical polymers in clinical drug delivery owing to its biocompatibility and biodegradability.However,en-dowing PEG-PLA micelles with high drug loading,self-assembly stability and fast intracellular drug re-lease is still challenging.Redox-responsive diblock copolymers(MPEG-SS-PMLA)of poly(ethylene glycol)and phenyl-functionalized poly(lactic acid)with disulfide bond as the linker are synthesized to prepare PLA-based micelles that demonstrate excellent colloidal stability and high Ru loading.Notably,MPEG-SS-PMLA achieved a remarkably high Ru loading efficiency of 84.3％due to the existence of strong π-πstacking between phenyl and Ru complex.MPEG-SS-PMLA exhibited good colloidal stability in physio-logical condition but quickly destabilized by reductive tumor microenvironment.Interestingly,about 74％of Ru complex was released under 10 mmol/L GSH concentration.Ru-loaded MEPG-SS-PMLA showed ef-ficient delivery and release of Ru complex into MCF-7 cancer cells,achieving enhanced in vitro and in vivo antitumor activity of photodynamic therapy.This feasible functionalization method of MPEG-PLA has appeared to be a clinically viable platform for controlled delivery therapeutic agents and enhanced pho-totherapy.