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

Yanan Li; Xiaolian Li; Yang Lu; Birendra Chaurasiya; Gujie Mi; Di Shi; Daquan Chen; Thomas J Webster; Jiasheng Tu; Yan Shen

doi:10.1016/j.nano.2019.102095

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

Nanomedicine. 2020 Jan:23:102095. doi: 10.1016/j.nano.2019.102095. Epub 2019 Oct 25.

Authors

Yanan Li¹, Xiaolian Li¹, Yang Lu², Birendra Chaurasiya¹, Gujie Mi³, Di Shi³, Daquan Chen⁴, Thomas J Webster⁵, Jiasheng Tu⁶, Yan Shen⁷

Affiliations

¹ Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
² Beijing University of Chinese Medicine, Beijing, China.
³ Department of Chemical Engineering, 313 Snell Engineering Center, Northeastern University, Boston, USA.
⁴ School of Pharmacy, Yantai University, Yantai, China.
⁵ Department of Chemical Engineering, 313 Snell Engineering Center, Northeastern University, Boston, USA. Electronic address: th.webster@neu.edu.
⁶ Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, China. Electronic address: jiashengtu@cpu.edu.cn.
⁷ Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, China. Electronic address: shenyan19820801@126.com.

PMID: 31669856
DOI: 10.1016/j.nano.2019.102095

Abstract

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.

Keywords: Antitumor; Cancer; DOX; Nanomedicine; Reverse multidrug resistance; Triterpenoids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Combined Chemotherapy Protocols* / chemistry
Antineoplastic Combined Chemotherapy Protocols* / pharmacology
Breast Neoplasms / drug therapy*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Cell Line, Tumor
Doxorubicin / chemistry
Doxorubicin / pharmacology
Drug Carriers* / chemistry
Drug Carriers* / pharmacology
Drug Resistance, Multiple / drug effects*
Drug Resistance, Neoplasm / drug effects*
Female
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Nanoparticles* / chemistry
Nanoparticles* / therapeutic use
Plant Extracts / chemistry
Plant Extracts / pharmacology
Wolfiporia / chemistry
Xenograft Model Antitumor Assays

Substances

Drug Carriers
Plant Extracts
Doxorubicin