Novel self-assembled amphiphilic mPEGylated starch-deoxycholic acid polymeric micelles with pH-response for anticancer drug delivery

Abstract

A novel amphiphilic polymer (mPEGylated starch-deoxycholic acid, mPEG-St-DCA) was successfully prepared by grafting hydrophobic deoxycholic acid (DCA) into mPEGylated starch. According to the characterization of ¹H NMR and FTIR, mPEG-St-DCA polymers could self-assemble into micelles with spherical core–shell structures. With the degree of substitution (DS) of DCA increasing, the average size of micelles (pH 7.4) decreased to below 200 nm. Correspondingly, the critical micelle concentration (CMC) decreased from 0.048 to 0.022 mg mL⁻¹. And zeta potential values were near −2 mV. But under the condition of pH 6.5, the size and CMC showed an increasing trend. Doxorubicin (DOX), a model anticancer drug, was efficiently loaded into mPEG-St-DCA micelles, and in vitro release exhibited that DOX-loaded micelles had a good in vitro pH-induced drug release. MTT assays confirmed that mPEG-St-DCA micelles were biocompatible with HeLa cells, and DOX-loaded micelles had a relatively better cytotoxicity against HeLa cells with a remarkably high IC₅₀ of 5.74 μg mL⁻¹. Confocal laser scanning microscopy (CLSM) analyses demonstrated that mPEG-St-DCA micelles could be internalized efficiently by HeLa cells to realize intracellular DOX release, which further enhanced the inhibition of cell proliferation. On the basis of the above results, it was indicated that novel amphiphilic mPEG-St-DCA micelles with pH-response could be used as drug delivery carriers for cancer therapy.