Biocompatible Reduction and pH Dual-Responsive Core Cross-Linked Micelles Based on Multifunctional Amphiphilic Linear–Hyperbranched Copolymer for Controlled Anticancer Drug Delivery

Abstract

Novel strategy has been developed for fabricating the biocompatible reduction and pH dual-responsive core cross-linked (CCL) micelles as drug delivery system (DDS) for the controlled anticancer drug delivery, via the atom transfer radical polymerization (ATRP) of <i>tert</i>-butyl acrylate (<i>t</i>BA) with <i>N</i>,<i>N</i>′-bis­(acryloyl)­cystamine (BACy) as cross-linker and a multifunctional amphiphilic linear–hyperbranched copolymer as macroinitiator, which was synthesized via the self-condensing vinyl copolymerization (SCVCP) of <i>t</i>BA and <i>p</i>-chloromethylstyrene (CMS) with a poly­(ethylene glycol) (PEG) based initiator (mPEG-Br). The hydrolyzed core cross-linked (HCCL) micelles were obtained as DDS for doxorubicin (DOX) by hydrolysis the <i>t</i>BA units into acrylic acid (AA) ones. The <i>in vitro</i> release performance showed that higher GSH concentration and/or lower pH value would lead to a faster and more efficient DOX release, meaning their reduction and pH dual-responsiveness. Therefore, the proposed HCCL micelles are expected to be potential anticancer drug-carriers for tumor microenvironment responsive controlled delivery