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

• Novel redox-responsive core-crosslinked mPEG-St-DPA micelles were prepared.
• mPEG-St-DPA micelles were stable, hemocompatible and biocompatible.
• mPEG-St-DPA micelles exhibited high drug loading capacity after crosslinking.
• mPEG-St-DPA micelles had a good redox-response for intracellular drug delivery.
• mPEG-St-DPA micelles hold great potential as ideal drug delivery carriers.

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.

Graphical AbstractA core-crosslinked redox-responsive polymeric micelles based on mPEG-St crosslinked by DPA with disulfide bond (mPEG-St-DPA) were reported, which had excellent stability, biocompatibility and hemocompatibility. DOX was used as a model drug and efficiently loaded into mPEG-St-DPA micelles. And the release of the encapsulated DOX was accelerated in the presence of GSH due to the cleavage of the disulfide bonds.Figure optionsDownload as PowerPoint slide