Photodynamic therapy-triggered on-demand drug release from ROS-responsive core-cross-linked micelles toward synergistic anti-cancer treatment

摘要

Polymeric micelles have demonstrated wide utility for chemodrug delivery,which however,still suffer from shortcomings such as undesired drug loading,disassembly upon dilution,pre-leakage of drug cargoes during systemic circulation,and lack of cancer-selective drug release.Herein,a poly(ethylene glycol) (PEG)-polyphosphoester-based,reactive oxygen species (ROS)-responsive,core-cross-linked (CCL) micellar system was developed to encapsulate both chemodrug (doxorubicin,Dox) and photosensitizer (chlorin e6,Ce6).The hydrophobic core of the micelles was cross-linked via a thioketal (TK)-containing linker,which notably enhanced the drug loading and micelle stability.In tumor cells,far-red light irradiation of Ce6 generated ROS to cleave the TK linkers and disrupt the micelle cores.As such,micelles were destabilized and Dox release was promoted,which thereafter imparted synergistic anti-cancer effect with ROS-mediated photodynamic therapy.This study provides an effective approach to realize the precise control over drug loading,formulation stability,and cancer-selective drug release using polymeric micelles,and would render promising utilities for the programmed anti-cancer combination therapy.