Quercetin and doxorubicin co-encapsulated biotin receptor-targeting nanoparticles for minimizing drug resistance in breast cancer
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Li Lv1,2,*, Chunxia Liu1,3,*, Chuxiong Chen2,*, Xiaoxia Yu2, Guanghui Chen2, Yonghui Shi2, Fengchao Qin2, Jiebin Ou2, Kaifeng Qiu2, Guocheng Li1,2
1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, China
2Department of Pharmacy, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, China
3Department of Pharmacy, Zengcheng District People's Hospital of Guangzhou, Guangzhou 511300, Guangdong, China
*These authors contributed equally to this work
Guocheng Li, email: [email protected]
Kaifeng Qiu, email: [email protected]
Keywords: biotin, doxorubicin, quercetin, co-delivery, drug resistance
Received: October 30, 2015 Accepted: March 14, 2016 Published: April 06, 2016
The combination of a chemotherapeutic drug with a chemosensitizer has emerged as a promising strategy for cancers showing multidrug resistance (MDR). Herein we describe the simultaneous targeted delivery of two drugs to tumor cells by using biotin-decorated poly(ethylene glycol)-b-poly(ε-caprolactone) nanoparticles encapsulating the chemotherapeutic drug doxorubicin and the chemosensitizer quercetin (BNDQ). Next, the potential ability of BNDQ to reverse MDR in vitro and in vivo was investigated. Studies demonstrated that BNDQ was more effectively taken up with less efflux by doxorubicin-resistant MCF-7 breast cancer cells (MCF-7/ADR cells) than by the cells treated with the free drugs, single-drug–loaded nanoparticles, or non-biotin–decorated nanoparticles. BNDQ exhibited clear inhibition of both the activity and expression of P-glycoprotein in MCF-7/ADR cells. More importantly, it caused a significant reduction in doxorubicin resistance in MCF-7/ADR breast cancer cells both in vitro and in vivo, among all the groups. Overall, this study suggests that BNDQ has a potential role in the treatment of drug-resistant breast cancer.
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