Redox-sensitive, PEG-shielded carboxymethyl PEI nanogels silencing MicroRNA-21, sensitizes resistant ovarian cancer cells to cisplatin
Redox-sensitive, PEG-shielded carboxymethyl PEI nanogels silencing MicroRNA-21, sensitizes resistant ovarian cancer cells to cisplatin
复制标题
DOI：
10.1016/j.ajps.2018.10.006
复制
发表时间：
2020-01-01
影响因子：
10.2
通讯作者：
Abolmaali, Samira Sadat
中科院分区：
文献类型：
--
作者：
Jauanmardi, Sanaz;Tamaddon, Ali Mohammad;Abolmaali, Samira Sadat
一系列支链聚乙烯亚胺 (PEI) 修饰，包括用于空间屏蔽的聚乙二醇化 (PEG2k-PEI)、用于合成 PEG2k-PEI-ss 纳米凝胶的氧化还原敏感交联以及随后用于调节聚合物 pka 的羧甲基化 (PEG2k-CMPEI-ss) 已被引入用于抗 miR-21 的细胞递送。使用 H-1 NMR、FTIR、TNBS、电位滴定、粒径和电位对合成进行了表征。通过凝胶阻滞、溴化乙锭染料排除、硫酸肝素竞争和 DNase I 消化实验研究了不同 N/P 比率下抗 miR-21 的负载。通过茎环RT PCR检测A2780卵巢癌细胞系中miR-21沉默是否对顺铂耐药敏感。已表明，在核酸负载、针对细胞外基质和核酸酶的保存以及体外 miRNA-21 的序列特异性沉默方面，PEG2k-CMPEI-ss 非常适合递送抗 miR-21。此外，已经证明，即使在无毒浓度下，用负载抗 miR-21 的纳米凝胶预处理细胞也可以使它们对 cis-Pt 敏感。结果表明，PEG2k-CMPEIss 介导的 microRNA 递送可被视为卵巢癌治疗的新策略。 (C) 2018 沉阳药科大学。由 Elsevier B.V. 出版
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 using H-1 NMR, FTIR, TNBS, potentiometric titration, particle size and 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 silencing 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 extracellular 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 sensitize them to cis-Pt even at non-toxic concentraions. The results indicate that PEG2k-CMPEIss mediated microRNA delivery can be considered as a novel strategy for ovarian cancer therapy. (C) 2018 Shenyang Pharmaceutical University. Published by Elsevier B.V.