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 biomedical polymers in clinical drug delivery owing to its biocompatibility and biodegradability. However, endowing PEG-PLA micelles with high drug loading, self-assembly stability and fast intracellular drug release 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-π stacking between phenyl and Ru complex. MPEG-SS-PMLA exhibited good colloidal stability in physiological 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 efficient 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 phototherapy.