國家衛生研究院 NHRI:Item 3990099045/5335
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    題名: Enhanced chemotherapy of cancer using pH-sensitive mesoporous silica nanoparticles to antagonize P-Glycoprotein-Mediated drug resistance
    作者: Huang, IP;Sun, SP;Cheng, SH;Lee, CH;Wu, CY;Yang, CS;Lo, LW;Lai, YK
    貢獻者: Division of Medical Engineering Research;Center for Nanomedicine Research
    摘要: Multidrug resistance (MDR) is the major clinical obstacle in management of cancer by chemotherapy. Overexpression of ATP-dependent efflux transporter P-glycoprotein (PGP) is a key factor contributing to multidrug resistance of cancer cells. The purpose of the present study was to use the endosomal pH-sensitive MSN (MSN-Hydrazone-Dox) for controlled release of doxorubicin (Dox) in an attempt to overcome the PGP-mediated MDR. In vitro cell culture studies indicate that uptake of MSN-Hydrazone-Dox by the human uterine sarcoma MES-SA/Dox-resistant tumor (MES-SA/Dx-5) cell occurs through endocytosis thus bypassing the efflux pump resistance. This improves the efficacy of the drug and leads to significant cytotoxicity and DNA fragmentation evidenced by TUNEL and DNA laddering assays. In vivo studies show that the intratumor injection of MSN-Hydrazone-Dox induces significant apoptosis of MES-SA/Dox-resistant cancer cells. This is validated by active caspase-3 immunohistochemical analysis. However, MSN-Hydrazone, without Dox-conjugation, cannot induce apoptosis in vitro and in vivo. In conclusion, both in vitro and in vivo studies show that MSN could serve as an efficient nanocarrier entering cell avidly via endocytosis, thus bypassing the PGP efflux pump to compromise the PGP-mediated MDR. MSN-Hydrazone-Dox could further respond to endosomal acidic pH to release Dox in a sustained manner. Besides the cell study, this is the first report that successfully demonstrates the therapeutic efficacy of using MSN against MDR cancer in vivo.
    日期: 2011-05
    關聯: Molecular Cancer Therapeutics. 2011 May;10(5):761-769.
    Link to: http://mct.aacrjournals.org/content/early/2011/03/16/1535-7163.MCT-10-0884
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1535-7163&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000291427000006
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79956028537
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