title: Gadolinium-conjugated PLA-PEG nanoparticles as liver targeted molecular MRI contrast agent.
abstract: A nanoparticle magnetic resonance imaging (MRI) contrast agent targeted to liver was developed by conjugation of gadolinium (Gd) chelate groups onto the biocompatible poly(l-lactide)-block-poly (ethylene glycol) (PLA-PEG) nanoparticles. PLA-PEG conjugated with diethylenetriaminopentaacetic acid (DTPA) was used to formulate PLA-PEG-DTPA nanoparticles by solvent diffusion method, and then Gd was loaded onto the nanoparticles by chelated with the unfolding DTPA on the surface of the PLA-PEG-DTPA nanoparticles. The mean size of the nanoparticles was 265.9 ± 6.7 nm. The relaxivity of the Gd-labeled nanoparticles was measured, and the distribution in vivo was evaluated in rats. Compared with conventional contrast agent (Magnevist), the Gd-labeled PLA-PEG nanoparticles showed significant enhancement both on liver targeting ability and imaging signal intensity. The T(1) and T(2) relaxivities per [Gd] of the Gd-labeled nanoparticles was 18.865 mM(-1) s(-1) and 24.863 mM(-1) s(-1) at 3 T, respectively. In addition, the signal intensity in vivo was stronger comparing with the Gd-DTPA and the T(1) weight time was lasting for 4.5 h. The liver targeting efficiency of the Gd-labeled PLA-PEG nanoparticles in rats was 14.57 comparing with Magnevist injection. Therefore, the Gd-labeled nanoparticles showed the potential as targeting molecular MRI contrast agent for further clinical utilization.
authors.affiliation: School of Pharmaceutical Science, Shandong University, Ji'nan, People's Republic of China.
authors.forename: Zhijin
authors.initials: Z
authors.lastname: Chen
authors.forename: Dexin
authors.initials: D
authors.lastname: Yu
authors.forename: Chunxi
authors.initials: C
authors.lastname: Liu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Chunhong
authors.initials: C
authors.lastname: Ma
authors.forename: Jibin
authors.initials: J
authors.lastname: Song
authors.forename: Zaijun
authors.initials: Z
authors.lastname: Lu
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D056945:Hep G2 Cells; D006801:Humans; D007773:Lactates / Q000138:chemical synthesis / Q000737:chemistry*; D008027:Light; D008099:Liver / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D057054:Molecular Imaging; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012542:Scattering, Radiation; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D001672:Biocompatible Materials; D003287:Contrast Media; D004337:Drug Carriers; D007773:Lactates; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; D005682:Gadolinium; D019786:Gadolinium DTPA