title: Modularly assembled magnetite nanoparticles enhance in vivo targeting for magnetic resonance cancer imaging.
abstract: Modularly assembled targeting nanoparticles were synthesized through self-assembly of targeting moieties on surfaces of functional nanoparticles. Specific molecular recognition of nickel nitrilotriacetate on Fe3O4 nanoparticles with hexahistidine tag on RGD4C peptides results in precisely controlled orientation of the targeting peptides. Better selectivity of the self-assembled RGD4C-Fe3O4 nanoparticles targeting oral cancer cells than that achievable through a conventional chemical cross-link strategy was demonstrated by means of atomic absorption spectrometry (AAS). An oral cancer hamster model was applied to reveal specific in vivo targeting and MR molecular imaging contrast in cancer lesions expressing alphavbeta3 integrin. Both AAS and MRI revealed that the self-assembled nanoparticles improved the targeting efficiency and reduced the hepatic uptake as compared with the conventional chemical cross-link particles. We investigated the biosafety, biodistribution, and kinetics of the nanoparticles and found that the nanoparticles were significantly cleared from the liver and kidneys after one week. By recombining the desired targeting moiety and various functional nanoparticles through self-assembly, this new modularly designed platform has the capability of enhancing the efficiency of targeted diagnosis and therapies for a wide spectrum of biomedical applications.
authors.affiliation: Institute of Basic Medical Sciences and Department of Chemistry, National Cheng Kung University, Tainan 701.
authors.forename: Ping-Ching
authors.initials: PC
authors.lastname: Wu
authors.forename: Chia-Hao
authors.initials: CH
authors.lastname: Su
authors.forename: Fong-Yu
authors.initials: FY
authors.lastname: Cheng
authors.forename: Jun-Cheng
authors.initials: JC
authors.lastname: Weng
authors.forename: Jyh-Horng
authors.initials: JH
authors.lastname: Chen
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Tsai
authors.forename: Chen-Sheng
authors.initials: CS
authors.lastname: Yeh
authors.forename: Wu-Chou
authors.initials: WC
authors.lastname: Su
authors.forename: Jih Ru
authors.initials: JR
authors.lastname: Hwu
authors.forename: Yonhua
authors.initials: Y
authors.lastname: Tzeng
authors.forename: Dar-Bin
authors.initials: DB
authors.lastname: Shieh
mesh_terms: D000042:Absorption; D000595:Amino Acid Sequence; D000818:Animals; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D052203:Ferrosoferric Oxide / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008422:Materials Testing; D051379:Mice; D009062:Mouth Neoplasms / Q000175:diagnosis; D053758:Nanoparticles / Q000737:chemistry*; D009532:Nickel / Q000737:chemistry; D009571:Nitrilotriacetic Acid / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D009842:Oligopeptides; D010456:Peptides, Cyclic; C047981:arginyl-glycyl-aspartic acid; D009532:Nickel; D009571:Nitrilotriacetic Acid; D052203:Ferrosoferric Oxide