A pH-responsive cyclodextrin-based hybrid nanosystem as a nonviral vector for gene delivery
A pH-responsive cyclodextrin-based hybrid nanosystem as a nonviral vector for gene delivery
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pH响应性环糊精混合纳米系统作为基因传递的非病毒载体
DOI：
10.1016/j.biomaterials.2013.02.035
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发表时间：
2013-05-01
期刊：
影响因子：
14
通讯作者：
Wang, Guansong
中科院分区：
文献类型：
--
作者：
Chen, Huaping;Liu, Xueping;Wang, Guansong
缺乏安全、高效、成本效益高和易于扩展的递送平台是限制寡核苷酸治疗药物床边翻译的最大障碍和关键问题之一。酸不稳定材料在开发非病毒载体方面特别有兴趣，因为它们能够在细胞内运送治疗有效载荷。在本研究中，通过将pH响应型环糊精材料与低分子量聚乙烯亚胺(PEI)相结合，设计了一种纳米矢量。通过纳米乳液技术可以将反义寡核苷酸(ASON)bc l-xl以极高的载药量包裹到该杂化纳米系统中。所开发的pH响应型反义寡核苷酸纳米药物能够以时间和剂量依赖的方式有效地转染人肺腺癌细胞，从而有效地抑制细胞生长，显著抑制Bclxl mRNA/蛋白的表达，并有效地诱导细胞凋亡。重要的是，与基于PLGA的对应载体和常用的阳离子载体如支化PEI(25000 Da)和Lipofetamine2000相比，新的纳米载体显示出显著更高的效率和更低的细胞毒性。这种pH响应型杂交纳米系统可能成为一种安全有效的非病毒载体，在基因治疗中可能会有广泛的应用。(C)2013爱思唯尔有限公司。保留所有权利。
The absence of safe, efficient, cost-effective, and easily scalable delivery platforms is one of the most significant hurdles and critical issues that limit the bench to bedside translation of oligonucleotides-based therapeutics. Acid-labile materials are of special interest in developing nonviral vectors due to their capability of intracellularly delivering therapeutic payload. In this study, a nanovector was designed by integrating a pH-responsive cyclodextrin material and low molecular weight polyethylenimine (PEI). Antisense oligonucleotide (ASON) Bcl-xl could be encapsulated into this hybrid nanosystem with extremely high loading efficiency by a nanoemulsion technique. The developed pH-responsive ASON nanotherapeutics could be efficiently transfected into human lung adenocarcinoma cells in a time- and dose-dependent manner, resulting in effective cell growth inhibition, significant suppression on the expression of Bcl-xl mRNA/protein, and efficient cell apoptosis. Importantly, the new nanovector showed drastically higher efficacy and lower cytotoxicity when compared with PLGA-based counterpart and commonly used cationic vectors like branched PEI (25,000 Da) and Lipofectamine 2000. This pH-responsive hybrid nanosystem may serve as a safe and efficient nonviral vector that may find wide applications in gene therapy. (C) 2013 Elsevier Ltd. All rights reserved.