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首页> 外文期刊>Journal of drug targeting >PK11195-chitosan-graft-polyethylenimine-modified SPION as a mitochondria-targeting gene carrier
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PK11195-chitosan-graft-polyethylenimine-modified SPION as a mitochondria-targeting gene carrier

机译:PK11195-壳聚糖 - 移植聚乙烯 - 改性的氨基氨基,作为线粒体靶向基因载体

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摘要

Superparamagnetic iron oxide nanoparticle (SPION) holds great potential as a gene delivery system due to its unique properties, such as good biocompatibility and non-invasive targeting ability. In this study, we modified SPION with chitosan-graft-PEI (CHI-g-PEI) and PK11195, to fabricate a mitochondria-targeting gene carrier, PK-CP-SPION. PK-CP-SPION manifested prominent physicochemical properties for magnetic guided gene delivery, and it could effectively condense and protect DNA at proper weight ratios. The in vitro cytotoxicity of PK-CP-SPIONs was mild. Under an external magnetic field, the transfection efficiency of PK-CP-SPIONs was comparable to PEI 25 K with shorter transfection time. PK11195 facilitated the specific accumulation of PK-CP-SPIONs in mitochondria, leading to the leakage of cytochrome c, the dissipation of mitochondrial membrane potential and subsequently the activation of mitochondria apoptosis pathway. These results indicated that with further development, PK-CP-SPIONs could serve as a multifunctional nanoplatform for magnetic targeting gene delivery and mitochondria-targeting therapy, leading enhanced therapeutic effect towards tumor cells.
机译:超顺磁性氧化铁纳米粒子(SpiON)由于其独特的性质,例如良好的生物相容性和非侵袭性靶向能力,具有巨大的潜力作为基因递送系统。在本研究中,我们用壳聚糖 - 移植物 - PEI(CHI-G-PEI)和PK11195进行了修饰的SPION,以制造线粒体靶向基因载体PK-CP-SPION。 PK-CP-SPION表现出磁导基因递送的突出物理化学性质,并且可以在适当的重量比下有效地凝结和保护DNA。 PK-CP酱的体外细胞毒性温和。在外部磁场下,PK-CP-CP-族的转染效率与PEI 25K相当,具有较短的转染时间。 PK11195促进了线粒体中PK-CP酱的特异性积累,导致细胞色素C的泄漏,线粒体膜电位的耗散,随后对线粒体凋亡途径的激活。这些结果表明,随着进一步的发展,PK-CP-酱可以用作磁性靶向基因递送和线粒体靶向治疗的多功能纳米片,引起肺部细胞的治疗效果。

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