Fabrication of dual-sensitive poly(β-hydroxyl amine) micelles for controlled drug delivery

Abstract

Development of multi-responsive biodegradable micellar drug delivery systems for targeted cancer chemotherapy remains a major challenge. Here we demonstrate a kind of pH and reduction dual-responsive cationic polymer via an effective amine–epoxy polymerization, which could self-assemble into the biodegradable micelles in an aqueous solution. On account of the tumor cells or tissues possessing low pH values and high concentrations of reductive agents, these micelles exhibited the specific tumor target ability and maximal drug-release controllability inside tumor cells upon changes in physical and chemical environments, but presented excellent stability at physiological conditions. CCK-8 assay showed that these DOX-loaded micelles had a similar cytotoxicity for MCF-7 tumor cells as the free DOX molecules while blank micelles were low toxic to the cells. Confocal laser scanning microscopy (CLSM) observation revealed that the drug-loaded micelles were quickly internalized by endosomes to effectively restrain the cancer cell growth. These results indicated these biodegradable micelles could be the novel and efficient dual-responsive nanocarriers to improve the drug delivery and enhance the antitumor efficacy.