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 tert-butyl acrylate (tBA) with N,N'-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 tBA and p-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 tBA units into acrylic acid (AA) ones. The in vitro 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.