title: Targeted RGD nanoparticles for highly sensitive in vivo integrin receptor imaging.
abstract: A new magnetic resonance imaging (MRI) contrast bearing RGD peptide is reported. In this study, ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles with various sizes were prepared. Particles sizes between 6 and 13 nm were tuned by varying the stirring rate. Remarkable negative contrast was observed because USPIO nanoparticles (13.1  ±  2.1 nm) generated high transversal relaxivity r₂ (188  ±  3 m m(-1)  s(-1) ) and saturation magnetization (94 emu g(-1) Fe). The USPIO nanoparticles were coated with PDA [2-(pyridyldithio)-ethylamine; PDA nanoparticles] containing functional polymer, which can be readily synthesized by Michael addition. The PDA nanoparticles were conjugated with RGD peptide (RGD nanoparticles) for targeting the specific site. The target specificity and high relaxivity allowed RGD nanoparticles to differentiate the expression level of integrin receptor on several cell lines and tumors (MCF-7, A-549, HT-29 and HT-1080) by in vitro and in vivo MR imaging. Importantly, a remarkable negative contrast (-51.3 ± 6.7%) was observed for in vivo MR imaging of MCF-7 tumor. This result implies that the RGD nanoparticles that greatly enhance the MR imaging are highly sensitive for early stage tumor detection.
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, 75 Bo-Ai Street, Hsinchu, 300, Taiwan.
authors.forename: Ren-Yen
authors.initials: RY
authors.lastname: Lin
authors.forename: Kasala
authors.initials: K
authors.lastname: Dayananda
authors.forename: Ting-Jung
authors.initials: TJ
authors.lastname: Chen
authors.forename: Chiao-Yun
authors.initials: CY
authors.lastname: Chen
authors.forename: Gin-Chung
authors.initials: GC
authors.lastname: Liu
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Lin
authors.forename: Yun-Ming
authors.initials: YM
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line / Q000378:metabolism; D045744:Cell Line, Tumor / Q000378:metabolism / Q000637:transplantation; D003287:Contrast Media / Q000032:analysis* / Q000138:chemical synthesis; D003911:Dextrans / Q000032:analysis*; D004220:Disulfides / Q000032:analysis; D016650:Fluorescein-5-isothiocyanate / Q000032:analysis; D016023:Integrins / Q000032:analysis*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000032:analysis*; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053761:Nanocomposites / Q000032:analysis*; D058726:Nanoconjugates / Q000032:analysis*; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000648:ultrastructure; D019301:Oleic Acid / Q000032:analysis; D009842:Oligopeptides / Q000032:analysis* / Q000138:chemical synthesis; D011725:Pyridines / Q000032:analysis
chemical_list: D003287:Contrast Media; D003911:Dextrans; D004220:Disulfides; D016023:Integrins; D058185:Magnetite Nanoparticles; D058726:Nanoconjugates; D009363:Neoplasm Proteins; D009842:Oligopeptides; D011725:Pyridines; C097921:ferumoxtran-10; D019301:Oleic Acid; C047981:arginyl-glycyl-aspartic acid; C055639:pyridyldithioethylamine; D016650:Fluorescein-5-isothiocyanate