Co-delivery of Poria cocos extract and doxorubicin as an ‘all-in-one’ nanocarrier to combat breast cancer multidrug resistance during chemotherapy

Recent studies have indicated that multidrug resistance (MDR) can significantly limit the effects of conventional chemotherapy. In this study, PT (Pachymic acid and dehydrotumulosic acid) are the two major triterpenoid components purified and identified in P. cocos. A liposomal co-delivery system encapsulating doxorubicin (DOX) and PT was prepared. Notably, the mechanism of PT reversed P-glycoprotein (P-gp) mediated MDR mainly relied on the inhibition of the P-gp function, which further decreased the levels of P-gp and caveolin-1 proteins. In drug-resistant MCF cells, co-administration with 5 μg/ml PT significantly enhanced sensitivity of DOX. Finally, liposome-mediated co-delivery with PT significantly improved the anti-tumor effect of DOX in tumor-bearing mice when compared to other single therapy groups. In conclusion, this study showed for the first time that DOX and PT act synergistically as an “all-in-one” treatment to reverse MDR during tumor treatment and, thus, should be studied further for a wide range of anti-cancer applications. Scheme 1 The pachymic acid and dehydrotumulosic acid extracted from Poria cocos could be used as a reversal drug resistance agent and were co-loaded with DOX in liposomes to reverse the resistance of tumor cells to chemotherapeutic drugs, achieving enhanced sensitized chemotherapy. [Display omitted]