SmartUnimolecular Micelle-Based Polyprodrug withDual-Redox Stimuli Response for Tumor Microenvironment: Enhanced inVivo Delivery Efficiency and Tumor Penetration

Low delivery efficiency and limited tumor penetration of nanoparticle-based drug delivery systems (DDSs), the two most concerned issues in tumor therapy, have been considered as the “Achilles’ heel” for tumor treatment. In this study, we have designed a highly sensitive dual-redox-responsive prodrug-based starlike polymer β-CD-b-P(CPTGSH-co-CPTROS-co-OEGMA) (CPGR) for synergistic chemotherapy. The high glutathione (GSH) concentration and high reactive oxygen species (ROS) levels are in a dynamic equilibrium in the tumor microenvironment (TME) and could trigger the disintegration of CPGR micelles, which can promote the release of anticancer drug camptothecin (CPT) completely and intelligently. In order to verify the synergistic antitumor mechanism, two corresponding single-responsive β-CD-b-P(CPTGSH-co-OEGMA) (CPG) and β-CD-b-P(CPTROS-co-OEGMA) (CPR) were altogether prepared as contrast. Both in vitro and in vivo studies confirmed the enhanced anticancer activity of CPGR micelles in comparison of single re...