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The HER2-Targeted Chemo-photothermal Combined Studies Of Aptamer-conjugated Mesoporous Silica-carbon Nanoparticles

Posted on:2016-07-16Degree:MasterType:Thesis
Country:ChinaCandidate:K Y WangFull Text:PDF
GTID:2371330464456363Subject:Pharmacy
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[Object]In this work,a new HB5 aptamer-functionalized mesoporous silica-carbon based doxorubicin(DOX)-loaded system(MSCN-PEG-HB5/DOX)was successfully constructed for chemophotothermal combined therapy of human epithelial growth factor receptor 2(HER2)-positive breast cancer cells.[Method]Drug release experiments of MSCN-PEG-HB5/DOX in vitro were conducted.HER2-positive breast cancer cells SK-BR-3 were used to evaluate thetargeting capability of HB5-modified nanoparticles in vitro.Targeting ability of HB5-modified drug delivery system also confirmed by in vivo imaging analysis.Cytotoxicity experiments were conducted to assess chemo-photothermal therapeutic effect.Toxic effects ofMSCN-based vectors in vitro and in vivo also need to be evaluated.[Results]The size of MSCN-PEG-HB5 nanoparticle was about 140 nm.The in vitro release result showed that MSCN-PEG-HB5/DOX exhibited pH-sensitive andNIR-triggered release manner.HB5-modified nanoparticles showed significant cellular uptake in HER2-positive breast cancer cellsin vitro and tumor sites in vivo.The intracellular uptake of functional nanoparticles was mainly based on the receptor-mediated mechanism.Moreover,cytotoxicity experiments demonstratedthat combined therapy induced highest cell killing effect compared to chemotherapy and photothermal therapy alone.The combination index(CI)was 0.253 indicating the synergistic effect of chemotherapy and photothermal therapy.No obvious toxicity ofMSCN-based nanoparticles was observed in vivo and in vitro.[Conclusion]DOX-loaded HB5-modified mesoporous silica-carbon based drug delivery system for combined therapy has been successfully prepared.Specific aptamer conjugated drug delivery system MSCN-PEG-HB5/DOX is a great platform for combined chemo-photothermal therapy targeted to HER2-positive cancers.
Keywords/Search Tags:HB5 aptamer, Mesoporous silica-carbon nanoparticles, Chemo-photothermal therapy, HER2-positive, Breast cancer
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