A TRACKABLE DRUG DELIVERY CARRIER MODIFIED WITH MITOCHONDRIAL TARGETING CONJUGATE FOR OVERCOMING DRUG RESISTANCE

Abstract

Fluorescent carbon quantum dots (CQDs) are considered as a good candidate for bioimaging as well as drug delivery system (DDS) due to their low cytotoxicity and high biocompatibility.1 D-α-tocopheryl polyethylene glycol succinate (TPGS), an inhibitor of P-glycoprotein (P-gp), has been used for developing a variety of TPGS-containing nanomedicines to overcome multidrug resistance (MDR) and enhance treatment efficacy in cancer chemotherapy. 2 In this work, a new DDS is constructed by using triphenylphosphine conjugated TPGS (TPP-TPGS) as a mitochondrial targeting modifier to functionalize oil-soluble CQDs and loading an anticancer drug, doxorubicin (DOX), in the bioconjugates of CQDs-TPGS-TPP. Accordingly, multi-functionalities (water-solubility, mitochondria-targeting, P-gp inhibition capability as well as imaging-trackable drug delivery property) are endowed to the as-formed DDS. Evaluations of cytotoxicity, cell imaging, and mitochondrial targeting were performed on the human breast cancer MCF-7 cell line. The TPP-modified DDS could be more uptaken by cells and preferentially distributed to the mitochondria. In DOX-resistant MCF-7 cells, an enhanced cytotoxicity was observed for the DDS loading with DOX (CQDs-TPGS-DOX-TPP) in comparison to free DOX and non-targeting conjugates (CQDs-TPGS-DOX). This work highlights promising application of the mitochondrial targeted DDS in reversing drug resistance in cancer therapy.