J Cancer 2019; 10(10):2357-2368. doi:10.7150/jca.30323

Research Paper

Co-delivery of Cyclopamine and Doxorubicin Mediated by Bovine Serum Albumin Nanoparticles Reverses Doxorubicin Resistance in Breast Cancer by Down-regulating P-glycoprotein Expression

Yong-lin Lu1,*, Ya-bin Ma2,*, Chan Feng1, Dong-lei Zhu1, Jie Liu1, Lv Chen1, Shu-jing Liang1✉, Chun-yan Dong1✉

1. Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China
2. Department of Pharmacy, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China
*Authors contributed equally to this work.

Abstract

Combination chemotherapy is considered to be one of the most effective treatments for breast cancer by reducing the emergence of drug resistance. In this study, a novel drug delivery system based on bovine serum albumin nanoparticles (BSA NPs) was successfully developed. Doxorubicin (DOX) and cyclopamine (CYC), a potential anti-cancer agent that inhibits the hedgehog signaling pathway were entrapped into BSA NPs through electrostatic interactions and hydrophobic interactions, respectively. Rather than simple combination of two different chemotherapeutics, the CYC also increased the intracellular DOX accumulation by decreasing the expression of P-glycoprotein (P-gp), which could thus reverse the DOX resistance. Tumor-targeting property of nanoparticles was the prerequisite for its further application. Interestingly, retention of fluorescently-labeled particles in vivo indicated that the dual-drug-loaded BSA NPs could not only target the primary tumors, but also target the metastatic lymph nodes, which would simultaneously inhibit the tumor growth and distant metastasis. Taken together, this study provides a promising strategy for co-delivery of drugs, tumor and metastatic lymph node targeting, and DOX resistance reversing in breast cancer chemotherapy.

Keywords: cyclopamine, doxorubicin, P-glycoprotein, bovine serum albumin nanoparticles, drug resistance

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How to cite this article:
Lu Yl, Ma Yb, Feng C, Zhu Dl, Liu J, Chen L, Liang Sj, Dong Cy. Co-delivery of Cyclopamine and Doxorubicin Mediated by Bovine Serum Albumin Nanoparticles Reverses Doxorubicin Resistance in Breast Cancer by Down-regulating P-glycoprotein Expression. J Cancer 2019; 10(10):2357-2368. doi:10.7150/jca.30323. Available from http://www.jcancer.org/v10p2357.htm