RVG-Peptide-Linked Trimethylated Chitosan for Delivery of siRNA to the Brain

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• 作者：Yikun Gao ; Zhan-You Wang ; Jinghai Zhang ; Youxi Zhang ; Hong Huo ; Tianyi Wang ; Tongying Jiang ; Siling Wang
• 刊名：Biomacromolecules
• 出版年：2014
• 出版时间：March 10, 2014
• 年：2014
• 卷：15
• 期：3
• 页码：1010-1018
• 全文大小：504K
• 年卷期：v.15,no.3(March 10, 2014)
• ISSN：1526-4602

文摘

In this work, a peptide derived from the rabies virus glycoprotein (RVG) was linked to siRNA/trimethylated chitosan (TMC) complexes through bifunctional PEG for efficient brain-targeted delivery of siRNA. The physiochemical properties of the complexes, such as siRNA complexing ability, size and 味 potential, morphology, serum stability, and cytotoxicity, were investigated prior to studying the cellular uptake, in vitro gene silencing efficiency, and in vivo biodistribution. The RVG-peptide-linked siRNA/TMC鈥揚EG complexes showed increased serum stability, negligible cytotoxicity, and higher cellular uptake than the unmodified siRNA/TMC鈥搈PEG complexes in acetylcholine receptor positive Neuro2a cells. The potent knockdown of BACE1, a therapeutic target in Alzheimer鈥檚 disease, demonstrated the gene silencing efficiency. In vivo imaging analysis showed significant accumulation of Cy5鈥搒iRNA in the isolated brain of mice injected with RVG-peptide-linked complexes. Therefore, the RVG-peptide-linked TMC鈥揚EG developed in this study can be used as a potential carrier for delivery of siRNA to the brain.