Polymeric Micelles with Reduction-Responsive Function for Targeted Cancer Chemotherapy

ACS Appl Bio Mater. 2020 Feb 17;3(2):1139-1146. doi: 10.1021/acsabm.9b01070. Epub 2020 Jan 21.

Abstract

In order to overcome the deficiencies of conventional nanotechnology-based drug delivery systems such as a short circulation time in blood, lack of tumor targeting, slow drug release in the interior of cancer cells, and so on, reduction-responsive polymeric micelles developed in this study with copolymers of TPGS3350-SS-DTX and TPGS3350-folate were triggered for cancer-targeted drug delivery. The layer of TPGS3350 in micelles was used to stabilize micelles and enhance the circulation period of micelles in blood. Once the micelles accumulated at the tumor region by EPR effect, tumor cells could ingest these micelles by the pathway of folate-receptor-mediated endocytosis. Next, fast drug release in cancer cells was achieved under the effect of high level of glutathione (GSH) inside cancer cells. The micelles invented in this study demonstrated various functions comprising active targeting, extended circulating life in blood, fast intracellular drug release, and so on. It can be noticed from findings in this research that these cooperative functions in micelles could significantly promote chemotherapeutic effectiveness and reduce their toxic side effects. Moreover, this work provides a drug delivery strategy to explore the feasibility of application reduction-responsive micelles for chemotherapy in clinic.

Keywords: cancer; chemotherapy; docetaxel; micelles; reduction-responsive.