title: Self-assembled nanoparticles based on the c(RGDfk) peptide for the delivery of siRNA targeting the VEGFR2 gene for tumor therapy.
abstract: The clinical application of small interfering RNA (siRNA) has been restricted by their poor intracellular uptake, low serum stability, and inability to target specific cells. During the last several decades, a great deal of effort has been devoted to exploring materials for siRNA delivery. In this study, biodegradable, tumor-targeted, self-assembled peptide nanoparticles consisting of cyclo(Arg-Gly-Asp-d-Phe-Lys)-8-amino-3,6-dioxaoctanoic acid-β-maleimidopropionic acid (hereafter referred to as RPM) were found to be an effective siRNA carrier both in vitro and in vivo. The nanoparticles were characterized based on transmission electron microscopy, circular dichroism spectra, and dynamic light scattering. In vitro analyses showed that the RPM/VEGFR2-siRNA exhibited negligible cytotoxicity and induced effective gene silencing. Delivery of the RPM/VEGFR2 (zebrafish)-siRNA into zebrafish embryos resulted in inhibition of neovascularization. Administration of RPM/VEGFR2 (mouse)-siRNA to tumor-bearing nude mice led to a significant inhibition of tumor growth, a marked reduction of vessels, and a down-regulation of VEGFR2 (messenger RNA and protein) in tumor tissue. Furthermore, the levels of IFN-α, IFN-γ, IL-12, and IL-6 in mouse serum, assayed via enzyme-linked immunosorbent assay, did not indicate any immunogenicity of the RPM/VEGFR2 (mouse)-siRNA in vivo. In conclusion, RPM may provide a safe and effective delivery vector for the clinical application of siRNAs in tumor therapy.
authors.affiliation: Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Chengdu Integrated TCM & Western Medicine Hospital, Chengdu, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: Institute of Neurosciences and the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, People's Republic of China.
authors.forename: Xialin
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Houliang
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Zhuomin
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Ji
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry*; D020868:Gene Silencing; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000235:genetics / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D009842:Oligopeptides; D034741:RNA, Small Interfering; C047981:arginyl-glycyl-aspartic acid; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: gene silencing; self-assembly nanoparticles; siRNA delivery; tumor targeting
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