RVG-Peptide-Linked Trimethylated Chitosan for Deliveryof siRNA to the Brain.

In this work, a peptide derived fromthe rabies virus glycoprotein(RVG) was linked to siRNA/trimethylated chitosan (TMC) complexes throughbifunctional PEG for efficient brain-targeted delivery of siRNA. Thephysiochemical properties of the complexes, such as siRNA complexingability, size and ζ potential, morphology, serum stability,and cytotoxicity, were investigated prior to studying the cellularuptake, in vitrogene silencing efficiency, and in vivobiodistribution. The RVG-peptide-linked siRNA/TMC–PEGcomplexes showed increased serum stability, negligible cytotoxicity,and higher cellular uptake than the unmodified siRNA/TMC–mPEGcomplexes in acetylcholine receptor positive Neuro2a cells. The potentknockdown of BACE1, a therapeutic target in Alzheimer’s disease,demonstrated the gene silencing efficiency. In vivoimaging analysis showed significant accumulation of Cy5–siRNAin the isolated brain of mice injected with RVG-peptide-linked complexes.Therefore, the RVG-peptide-linked TMC–PEG developed in thisstudy can be used as a potential carrier for delivery of siRNA tothe brain. [ABSTRACT FROM AUTHOR]