Abstract
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.
Keywords:
biotin; co-delivery; doxorubicin; drug resistance; quercetin.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B / antagonists & inhibitors
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ATP Binding Cassette Transporter, Subfamily B / metabolism
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Animals
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Antineoplastic Combined Chemotherapy Protocols / chemistry
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Antineoplastic Combined Chemotherapy Protocols / metabolism
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Biotin / chemistry
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Biotin / metabolism*
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Doxorubicin / chemistry
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Doxorubicin / metabolism
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Doxorubicin / pharmacology*
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Drug Carriers*
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Drug Compounding
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Drug Liberation
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Drug Resistance, Multiple / drug effects*
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Drug Resistance, Neoplasm / drug effects*
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Ethylene Glycols / chemistry*
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Female
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Humans
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Kinetics
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MCF-7 Cells
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Mice, Inbred BALB C
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Mice, Nude
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Nanoparticles*
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Polyesters / chemistry*
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Quercetin / chemistry
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Quercetin / metabolism
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Quercetin / pharmacology*
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Receptors, Growth Factor / metabolism*
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Solubility
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Xenograft Model Antitumor Assays
Substances
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ABCB1 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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Drug Carriers
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Ethylene Glycols
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Polyesters
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Receptors, Growth Factor
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biotin receptor
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poly(epsilon-caprolactone)-b-poly(ethylene glycol)
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Biotin
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Doxorubicin
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Quercetin