ZnO-Embedded Polymer Micelles as a Responsive Drug Delivery Carrier for Breast Cancer Therapy

Polymer micelles are currently the materials of choice for sustained-drug-release formulations due to their rich functionality. The existing polymer micelles suffer from limitations in low drug delivery. Here, we control the expansion degree of polymer micelles by introducing zinc oxide nanoparticles into the block copolymer micelles to achieve the pH response release of drugs. The poly[(4-(2-hydroxy-ethoxy) benzaldehyde) ether methacrylate]-block-poly[poly(ethylene glycol) methyl ether methacrylate] (PMBA-b-PEGA) block copolymer, which contains aldehyde groups, was synthesized using reversible addition–fragmentation chain transfer (RAFT) polymerization. The PMBA-b-PEGA block copolymer can self-assemble into polymer micelles in a selective solvent. In order to control the expansion of polymer micelles, the polymer hybrid micelles ((ZnO-N)-PMBA-b-PEGA) were formed by cross-linking the polymer micelles with amino-modified ZnO nanoparticles. The polymer hybrid micelles were loaded with doxorubicin (DOX) as a model drug. The expansion degree of DOX-loaded (ZnO-N)-PMBA-b-PEGA changes with an increase in acidity, and its particle size becomes larger with an increase of acidity. The particle size of DOX-loaded (ZnO-N)-PMBA-b-PEGA at pH 5.0 is 7 times larger than that at pH 7.4. As a result, the DOX-loaded (ZnO-N)-PMBA-b-PEGA system demonstrated pH-responsive drug release behavior, with the DOX achieving a maximum release of 49% at pH 5.0. In vivo studies have shown that DOX-loaded (ZnO-N)-PMBA-b-PEGA has an inhibitory effect on tumors in a mouse model of breast cancer. The polymer hybrid micelles generated in this work could thus have application as, for instance, the development of drug delivery system to treat breast cancer.