[Vascular endothelial cells targeted Tyr-RGD-PEG-PEI nano-drug synthesis and its biological activity].
The study is designed to synthesize nano-carrier Tyr-RGD (cyclo-[Arg-Gly-Asp-d-Tyr-Lys]) and poly(ethylene glycol) modified polyethylenimine (Tyr-RGD-PEG-PEI) targeting vascular endothelial cells, then analyze its nanoparticle properties and the characteristics of drug carrying and targeting properties in vivo / in vitro tumor. The nano-carrier Tyr-RGD-PEG-PEI was synthesized with the method of chemical synthesis and the properties of this nanoparticle and drug carrying characteristics were identified. Its effect of targeting vascular endothelial cells in vitro was studied with the method of competitive binding assay. The fluorescent labeled nano-drug was injected into tumor-bearing nude mice to observe its tumor-targeting. The mean size of nano-carrier Tyr-RGD-PEG-PE was about 145 nm, good in encapsulation efficiency of siRNA. After incubation in plasma for half an hour, only about 3 percent of siRNA out. It was confirmed that it was a single spot with TLC analysis, the R(f) value was 0.65. Receptor competition experiments showed that the nano could effectively compete with RGD in binding the receptors on endothelial cells. Tumor-bearing nude mice experiments showed that when containing a fluorescent-labeled siRNA of Tyr-RGD-PEG-PEI nano-drug was injected into mice, after 24 hours this nano-drug mainly distributed within the tumor tissue. However, nano-drug without Tyr-RGD appeared in tumor tissue as well as other organs such as livers, lungs, etc. The Tyr-RGD-targeted gene vector Tyr-RGD-PEG-PEI synthesized in this study has good nanoparticle properties and high efficiency of gene-drug encapsulation. Study of nude mice shows that the ability of its tumor-targeting is significantly better than nano-drug without Tyr-RGD.
Gao
Yong
Y
Department of Oncology, Shanghai East Hospital, Tongji University, Shanghai 200120, China. gaoyon@gmail.com
He
Sheng-Li
SL
Zhong
Gao-Ren
GR
Cai
Hong-Pei
HP
Li
Qi
Q
D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D016023:Integrins / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D034741:RNA, Small Interfering
D016023:Integrins; D009842:Oligopeptides; D034741:RNA, Small Interfering; C047981:arginyl-glycyl-aspartic acid