A pH-responsive cyclodextrin-based hybrid nanosystem as a nonviral vector for gene delivery

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• 作者：Huaping Chen^a ; ¹ ; Xueping Liu^a ; ¹ ; Yin Dou^b ; ¹ ; Binfeng He^a ; Li Liu^a ; Zhenghua Wei^a ; Jin Li^a ; Changzheng Wang^a ; Chengde Mao^c ; Jianxiang Zhang^b ; ^{jxzhang1980@gmail.com} ; ^{jxzhang@tmmu.edu.cn} ; Guansong Wang^a ; ^{wanggs2003@163.com}
• 关键词：Nanovector ; pH-responsive ; Cyclodextrin ; Antisense therapy ; Nanomedicine
• 刊名：Biomaterials
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：34
• 期：16
• 页码：4159-4172
• 全文大小：2054 K

文摘

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.