Liposomal Codelivery of Doxorubicin and Curcumin Sensitizes Antitumor Activity and Reduces Tumor Metastasis.

Abstract

Multidrug resistance (MDR) is a major obstacle to traditional cancer treatment using chemotherapeutic agents like doxorubicin (DOX). MDR affects drug dosage regimens and enables the recurrence and metastasis of cancer. Because DOX causes severe side effects at high dosages, it is important to use an MDR modulator to make cancer cells sensitive to DOX. This work focused on a liposome-based codelivery system containing curcumin (CUR) and DOX, focusing on CUR as an MDR modulator. The synergistic effect was maximized when the ratio of DOX and CUR was 1:1, and the synthesis of liposomal drugs was successfully verified. In addition, a successful MDR reversal effect was demonstrated through rhodamine 123 assay, Western blotting, and immunofluorescence. Compared to the conventional DOX treatment, the dual-drug treatment exhibits a significantly improved anticancer effect. In the murine metastasis 4T1 IP tumor model, the dual-drug-encapsulating liposomes successfully suppressed tumor growth and reversed the tumoral effect (omental tumor metastasis, fat, and muscle weight loss) into a normal state.