title: Conjugation of iron oxide nanoparticles with RGD-modified dendrimers for targeted tumor MR imaging.
abstract: This article reports a new approach for the synthesis of ultrasmall iron oxide nanoparticles (NPs) conjugated with Arg-Gly-Asp (RGD)-modified dendrimers (G5.NHAc-RGD-Fe3O4 NPs) as a platform for targeted magnetic resonance (MR) imaging of C6 glioma cells. Ultrasmall Fe3O4 NPs synthesized via a solvothermal route were conjugated with RGD peptide-modified generation-5 poly(amidoamine) dendrimers (G5.NH2-RGD). The final G5.NHAc-RGD-Fe3O4 NPs were formed following the acetylation of the remaining dendrimer terminal amines. The as-prepared multifunctional Fe3O4 NPs were characterized using various techniques. The results of a cell viability assay, cell morphological observation, and hemolysis assay indicated that the G5.NHAc-RGD-Fe3O4 NPs exhibit excellent cytocompatibility and hemocompatibility over the studied concentration range. In addition, RGD conjugated onto the Fe3O4 NPs allows for the efficient targeting of the particles to C6 cells that overexpress αvβ3 receptors, which was confirmed via in vitro cell MR imaging and cellular uptake. Finally, the G5.NHAc-RGD-Fe3O4 NPs were used in the targeted MR imaging of C6 glioma cells in mice. The results obtained from the current study indicate that the developed G5.NHAc-RGD-Fe3O4 NPs offer significant potential for use as contrast agents in the targeted MR imaging of different types of tumors.
authors.affiliation: Department of Radiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai 200080, P. R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Xu
authors.forename: Jingchao
authors.initials: J
authors.lastname: Li
authors.forename: Zaixian
authors.initials: Z
authors.lastname: Zhang
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.forename: Mingwu
authors.initials: M
authors.lastname: Shen
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
authors.forename: Guixiang
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D050091:Dendrimers / Q000737:chemistry*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D052203:Ferrosoferric Oxide / Q000737:chemistry; D005910:Glioma / Q000175:diagnosis / Q000000981:diagnostic imaging*; D006461:Hemolysis / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry; D011859:Radiography; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D001672:Biocompatible Materials; D003287:Contrast Media; D050091:Dendrimers; D009842:Oligopeptides; C531249:Poly(amidoamine); D011073:Polyamines; C047981:arginyl-glycyl-aspartic acid; D052203:Ferrosoferric Oxide
keywords: MR imaging; RGD; cancer cells; dendrimer; ultrasmall iron oxide nanoparticles