Redox-responsive core-cross-linked mPEGylated starch micelles as nanocarriers for intracellular anticancer drug release

Novel redox-responsive core-cross-linked polymers were prepared by cross-linking mPEGylated starch (mPEG-St) with 3,3′-dithiodipropionic acid (DPA), a cross-linker containing a disulfide bond. The structure of the polymer based on starch (mPEG-St-DPA) was characterized using nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), and Raman spectroscopy. In addition, these polymers could self-assemble into micelles in phosphate-buffered saline (PBS) solution. The size and critical micelle concentration (CMC) of the mPEG-St-DPA micelles decreased with an increase in the degree of cross-linking. Interestingly, the size of the mPEG-St-DPA micelles increased gradually in the presence of 10   mM glutathione (GSH) owing to the cleavage of the disulfide bonds in the micellar core. The mPEG-St-DPA micelles showed good stability, exhibiting slight changes in size after 1000-fold dilution with PBS solution or 10-fold dilution with dimethyl formamide (DMF). The results of a protein adsorption test indicated that the mPEG-St-DPA micelles were hemocompatible. Doxorubicin (DOX), a model anticancer drug, was efficiently loaded into the mPEG-St-DPA micelles. The in vitro release studies revealed that the DOX-loaded mPEG-St-DPA micelles showed enhanced release of DOX in the presence of GSH. An in vitro MTT assay confirmed that the core-cross-linked mPEG-St-DPA micelles were biocompatible with HeLa cells, and the DOX-loaded mPEG-St-DPA micelles displayed higher inhibition of HeLa cell proliferation. These results suggest that the redox-responsive mPEG-St-DPA micelles hold great potential as ideal drug delivery carriers for cancer therapy.