title: RVG-peptide-linked trimethylated chitosan for delivery of siRNA to the brain.
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.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, China.
authors.forename: Yikun
authors.initials: Y
authors.lastname: Gao
authors.forename: Zhan-You
authors.initials: ZY
authors.lastname: Wang
authors.forename: Jinghai
authors.initials: J
authors.lastname: Zhang
authors.forename: Youxi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Huo
authors.forename: Tianyi
authors.initials: T
authors.lastname: Wang
authors.forename: Tongying
authors.initials: T
authors.lastname: Jiang
authors.forename: Siling
authors.initials: S
authors.lastname: Wang
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D001921:Brain / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006023:Glycoproteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D011820:Rabies virus / Q000235:genetics; D014018:Tissue Distribution; D014764:Viral Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*
chemical_list: D006023:Glycoproteins; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D014764:Viral Proteins; C583075:rabies virus glycoprotein peptide; D048271:Chitosan; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human