4.3 Article

Quercetin and doxorubicin co-encapsulated biotin receptor-targeting nanoparticles for minimizing drug resistance in breast cancer

Journal

ONCOTARGET
Volume 7, Issue 22, Pages 32184-32199

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8607

Keywords

biotin; doxorubicin; quercetin; co-delivery; drug resistance

Funding

  1. National Natural Science Foundation of China [81503001]
  2. Guangdong Natural Science Foundation [2014A030310394]
  3. Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology [[2013]163]
  4. key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Insitutes [KLB09001]

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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(epsilon-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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