Modularly assembled magnetite nanoparticles enhance in vivo targeting for magnetic resonance cancer imaging.
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.
Wu
Ping-Ching
PC
Institute of Basic Medical Sciences and Department of Chemistry, National Cheng Kung University, Tainan 701.
Su
Chia-Hao
CH
Cheng
Fong-Yu
FY
Weng
Jun-Cheng
JC
Chen
Jyh-Horng
JH
Tsai
Tsung-Lin
TL
Yeh
Chen-Sheng
CS
Su
Wu-Chou
WC
Hwu
Jih Ru
JR
Tzeng
Yonhua
Y
Shieh
Dar-Bin
DB
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
D009842:Oligopeptides; D010456:Peptides, Cyclic; C047981:arginyl-glycyl-aspartic acid; D009532:Nickel; D009571:Nitrilotriacetic Acid; D052203:Ferrosoferric Oxide