Liposome-based codelivery of doxorubicin and curcumin for overcoming multi-drug resistance

Abstract

Multidrug resistance (MDR) caused by repeated chemotherapeutic treatment is a major obstacle to the traditional cancer treatment using chemotherapeutic agents like doxorubicin (DOX). This is because MDR not only affects drug dosing regimens, resulting in high doses of anticancer drugs, but also allows cancer recurrence and metastasis. Because DOX can cause severe side effects when administered at high doses, it is important to use MDR modulator to make cells sensitive to DOX. In this work, we focused on liposome-based codelivery system containing curcumin (CUR) and DOX, focusing on CUR as an MDR modulator. Especially, it was demonstrated through in vitro experiments that the synergistic effect is maximized when the ratio of DOX and CUR is 1:1. The synthesis of liposomal drugs at this optimal ratio was confirmed through dynamic light scattering (DLS) and high-performance liquid chromatography (HPLC). In addition, the successful MDR reversal effect and the ability to induce immunogenic cell death were demonstrated through rhodamine 123 (Rh123) assay, western blotting and immunofluorescence. Compared to the conventional DOX treatment, the dual drug treatment exhibits not only significantly improved anticancer effect but also outstanding immune responses.