RVG-Peptide-Linked Trimethylated Chitosan for Delivery of siRNA to the Brain
- 18 February 2014
- journal article
- Published by American Chemical Society (ACS) in Biomacromolecules
- Vol. 15 (3), 1010-1018
- https://doi.org/10.1021/bm401906p
Abstract
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 ζ 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–PEG complexes showed increased serum stability, negligible cytotoxicity, and higher cellular uptake than the unmodified siRNA/TMC–mPEG complexes in acetylcholine receptor positive Neuro2a cells. The potent knockdown of BACE1, a therapeutic target in Alzheimer’s disease, demonstrated the gene silencing efficiency. In vivo imaging analysis showed significant accumulation of Cy5–siRNA in the isolated brain of mice injected with RVG-peptide-linked complexes. Therefore, the RVG-peptide-linked TMC–PEG developed in this study can be used as a potential carrier for delivery of siRNA to the brain.Keywords
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