Co-delivery of Cyclopamine and Doxorubicin Mediated by Bovine Serum Albumin Nanoparticles Reverses Doxorubicin Resistance in Breast Cancer by Down-regulating P-glycoprotein Expression
Identifieur interne : 000946 ( Main/Merge ); précédent : 000945; suivant : 000947Co-delivery of Cyclopamine and Doxorubicin Mediated by Bovine Serum Albumin Nanoparticles Reverses Doxorubicin Resistance in Breast Cancer by Down-regulating P-glycoprotein Expression
Auteurs : Yong-Lin Lu [République populaire de Chine] ; Ya-Bin Ma [République populaire de Chine] ; Chan Feng [République populaire de Chine] ; Dong-Lei Zhu [République populaire de Chine] ; Jie Liu [République populaire de Chine] ; Lv Chen [République populaire de Chine] ; Shu-Jing Liang [République populaire de Chine] ; Chun-Yan Dong [République populaire de Chine]Source :
- Journal of Cancer [ 1837-9664 ] ; 2019.
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
Url:
DOI: 10.7150/jca.30323
PubMed: 31258739
PubMed Central: 6584414
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PMC:6584414Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Co-delivery of Cyclopamine and Doxorubicin Mediated by Bovine Serum Albumin Nanoparticles Reverses Doxorubicin Resistance in Breast Cancer by Down-regulating P-glycoprotein Expression</title><author><name sortKey="Lu, Yong Lin" sort="Lu, Yong Lin" uniqKey="Lu Y" first="Yong-Lin" last="Lu">Yong-Lin Lu</name><affiliation wicri:level="1"><nlm:aff id="A1">Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Ya Bin" sort="Ma, Ya Bin" uniqKey="Ma Y" first="Ya-Bin" last="Ma">Ya-Bin Ma</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Pharmacy, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pharmacy, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author><author><name sortKey="Feng, Chan" sort="Feng, Chan" uniqKey="Feng C" first="Chan" last="Feng">Chan Feng</name><affiliation wicri:level="1"><nlm:aff id="A1">Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author><author><name sortKey="Zhu, Dong Lei" sort="Zhu, Dong Lei" uniqKey="Zhu D" first="Dong-Lei" last="Zhu">Dong-Lei Zhu</name><affiliation wicri:level="1"><nlm:aff id="A1">Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Jie" sort="Liu, Jie" uniqKey="Liu J" first="Jie" last="Liu">Jie Liu</name><affiliation wicri:level="1"><nlm:aff id="A1">Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Lv" sort="Chen, Lv" uniqKey="Chen L" first="Lv" last="Chen">Lv Chen</name><affiliation wicri:level="1"><nlm:aff id="A1">Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author><author><name sortKey="Liang, Shu Jing" sort="Liang, Shu Jing" uniqKey="Liang S" first="Shu-Jing" last="Liang">Shu-Jing Liang</name><affiliation wicri:level="1"><nlm:aff id="A1">Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author><author><name sortKey="Dong, Chun Yan" sort="Dong, Chun Yan" uniqKey="Dong C" first="Chun-Yan" last="Dong">Chun-Yan Dong</name><affiliation wicri:level="1"><nlm:aff id="A1">Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31258739</idno><idno type="pmc">6584414</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584414</idno><idno type="RBID">PMC:6584414</idno><idno type="doi">10.7150/jca.30323</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000644</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000644</idno><idno type="wicri:Area/Pmc/Curation">000644</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000644</idno><idno 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Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Ya Bin" sort="Ma, Ya Bin" uniqKey="Ma Y" first="Ya-Bin" last="Ma">Ya-Bin Ma</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Pharmacy, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pharmacy, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author><author><name sortKey="Feng, Chan" sort="Feng, Chan" uniqKey="Feng C" first="Chan" last="Feng">Chan Feng</name><affiliation wicri:level="1"><nlm:aff id="A1">Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author><author><name sortKey="Zhu, Dong Lei" sort="Zhu, Dong Lei" uniqKey="Zhu D" first="Dong-Lei" last="Zhu">Dong-Lei Zhu</name><affiliation wicri:level="1"><nlm:aff id="A1">Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Jie" sort="Liu, Jie" uniqKey="Liu J" first="Jie" last="Liu">Jie Liu</name><affiliation wicri:level="1"><nlm:aff id="A1">Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Lv" sort="Chen, Lv" uniqKey="Chen L" first="Lv" last="Chen">Lv Chen</name><affiliation wicri:level="1"><nlm:aff id="A1">Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author><author><name sortKey="Liang, Shu Jing" sort="Liang, Shu Jing" uniqKey="Liang S" first="Shu-Jing" last="Liang">Shu-Jing Liang</name><affiliation wicri:level="1"><nlm:aff id="A1">Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author><author><name sortKey="Dong, Chun Yan" sort="Dong, Chun Yan" uniqKey="Dong C" first="Chun-Yan" last="Dong">Chun-Yan Dong</name><affiliation wicri:level="1"><nlm:aff id="A1">Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Breast Cancer Center, Shanghai East Hospital, Tongji University, Shanghai 200120</wicri:regionArea><wicri:noRegion>Shanghai 200120</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of Cancer</title><idno type="eISSN">1837-9664</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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 <italic>in vivo</italic> 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ferlay, J" uniqKey="Ferlay J">J Ferlay</name></author><author><name sortKey="Soerjomataram, I" uniqKey="Soerjomataram I">I Soerjomataram</name></author><author><name sortKey="Dikshit, R" uniqKey="Dikshit R">R Dikshit</name></author><author><name sortKey="Eser, S" uniqKey="Eser S">S Eser</name></author><author><name sortKey="Mathers, C" uniqKey="Mathers C">C Mathers</name></author><author><name sortKey="Rebelo, M" uniqKey="Rebelo M">M Rebelo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Lj" uniqKey="Yang L">LJ Yang</name></author><author><name sortKey="Gao, Y" uniqKey="Gao Y">Y Gao</name></author><author><name sortKey="Liu, Jj" uniqKey="Liu J">JJ 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