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Redox-sensitive,PEG-shielded carboxymethyl PEI nanogels silencing MicroRNA-21,sensitizes resistant ovarian cancer cells to cisplatin

摘要A series of branched polyethylenimine(PEI)modifications including PEGylation(PEG2k-PEI)for steric shielding,redox-sensitive crosslinking for synthesis PEG2k-PEI-ss nanogels and subsequent carboxymethylation(PEG2k-CMPEI-ss)for modulation of the polymer pka have been introduced for cellular delivery of Anti-miR-21.The synthesis was characterized us-ing 1H NMR,FTIR,TNBS,potentiometric titration,particle size and ζ potential.Loading of Anti-miR-21 at various N/P ratios was investigated by gel retardation,ethidium bromide dye exclusion,heparin sulfate competition and DNase I digestion experiments.The miR-21 si-lencing was measured by stem-loop RT PCR in A2780 ovarian cancer cell lines whether it is sensitive to resistant to cisplatin.It has been shown that PEG2k-CMPEI-ss was well suited for delivery of Anti-miR-21 in terms of nucleic acid loading,preservation against extracellu-lar matrix and nucleases and sequence-specific silencing of miRNA-21 in vitro.Moreover,it has been demonstrated that pre-treating cells with Anti-miR-21 loaded nanogels can sensi-tize them to cis-Pt even at non-toxic concentraions.The results indicate that PEG2k-CMPEI-ss mediated microRNA delivery can be considered as a novel strategy for ovarian cancer therapy.

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作者 Sanaz Javanmardi [1] Ali Mohammad Tamaddon [2] Mahmoud Reza Aghamaali [1] Ladan Ghahramani [3] Samira Sadat Abolmaali [2] 学术成果认领
作者单位 Department of Biology,Faculty of Science,University of Guilan,Rasht 64891,Iran [1] Center for Nanotechnology in Drug Delivery,Shiraz University of Medical Sciences,Shiraz 71345,Iran;School of Pharmacy,Shiraz University of Medical Sciences,Shiraz 71345,Iran [2] Center for Nanotechnology in Drug Delivery,Shiraz University of Medical Sciences,Shiraz 71345,Iran [3]
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发布时间 2021-12-02(万方平台首次上网日期,不代表论文的发表时间)
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亚洲药物制剂科学(英文版)

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