Fabrication of Polymer Micelles with Zwitterionic Shell and Biodegradable Core for Reductively Responsive Release of Doxorubicin

Abstract

To achieve a high stability in physiological environment and rapid intracellular drug release, a biodegradable zwitterionic triblock copolymer with a disulfide-linked poly-ε-caprolactone and polycarboxybetaine methacrylate (PCBMA-SS-PCL-SS-PCBMA) was prepared for micellar carrier to delivery doxorubicin (DOX) into tumor cells. PCBMA-SS-PCL-SS-PCBMA was obtained by following steps: i) introducing disulfide bonds through end-group modification of PCL diol with cystamine dihydrochloride; ii) preparing PCL-RAFT macromolecular chain transfer agent by EDC/NHS chemistry; iii) RAFT polymerization of zwitterionic monomer. Self-assembling from PCBMA-SS-PCL-SS-PCBMA, polymeric micelles had many advantages, such as ultra-low protein absorption in serum and obvious reduction-responsiveness in the presence of DTT. Furthermore, DOX-loaded micelles exhibited high stability upon centrifugation and lyophilization, a fast intracellular drug release and enhanced drug efficacy due to GSH-triggered PCBMA shell shedding and micellar reassembling. Thus, the polymeric micelles integrated several functions and properties could be prospectively utilized as valuable nanocarriers in cancer chemotherapeutics.