Redox-Responsive Amphipathic Dextran Nanomicelles for Solid Tumor Therapy

A disulfide bond containing deoxycholic acid-grafted dextran (Dex-SSDCA) was successfully prepared for drug delivery. The Dex-SSDCA polymers can self-assemble into nanomicelles at concentrations below 56 g/mL and encapsulate doxorubicin (DOX) effectively. When exposed to 10 mM Dithiothreitol (DTT), the nanomicelles disassembled rapidly and released DOX immediately. The DOX-loaded Dex-SSDCA nanomicelles were able to reverse the drug resistance of MCF-7/Adr cells and inhibit their growth in vitro. Moreover, DOX-loaded Dex-SSDCA nanomicelles could significantly suppress the growth of subcutaneous SKOV-3 ovarian cancer in vivo, exerting stronger efficiency on inhibiting tumor angiogenesis and proliferation while aggravating apoptosis of tumor cells, in comparison with the negative control and free DOX. The in vivo toxicity evaluation demonstrated that the Dex-SSDCA micelles reduced DOX-induced side effects. This redox-responsive amphipathic dextran is able to enhance the antitumor efficiency and reduce the toxicity of doxorubicin, thus has a potential as a drug carrier for cancer therapy.