pH- and redox-responsive self-assembly of amphiphilic hyperbranched poly(amido amine)s for controlled doxorubicin delivery

Abstract

Vinyl-terminated hyperbranched poly(amido amine)s is obtained by Michael addition polymerization of 4-(aminomethyl)piperidine (AMPD) with a double molar N,N-cystaminebis(acrylamide) (BAC). Then an amphiphilic hyperbranched poly(BAC2-AMPD1)-PEG is produced via converting the vinyl groups to amines followed by PEGylation. Transmission electron microscopy (TEM), dynamic light scattering (DLS), and ¹H nuclear magnetic resonance (NMR) results indicate that the micelles can be obtained via self-assembly of hyperbranched poly(BAC2-AMPD1)-PEG. Further an anti-cancer drug, doxorubicin (DOX), can be loaded into the micelles. pH- and redox-response of the micelles of hyperbranched poly(BAC2-AMPD1)-PEG without and with DOX are investigated. The results of confocal microscopy and flow cytometry reflect that FITC tagged or DOX loaded micelles of hyperbranched poly(BAC2-AMPD1)-PEG can enter HepG2 and MCF-7 cells, and DOX can be observed in the nucleus of the cells. The cytotoxicity of the micelles without and with DOX is evaluated in HepG2 and MCF-7 cells, and the efficacy to kill the cancer cells is discussed in comparison with free DOX.