title: Fabrication and evaluation of tumor-targeted positive MRI contrast agent based on ultrasmall MnO nanoparticles.
abstract: Gd(III) chelate is currently used as positive magnetic resonance imaging (MRI) contrast agent in clinical diagnosis, but generally induces the risk of nephrogenic systemic fibrosis (NSF) due to the dissociated Gd(3+) from Gd(III) chelates. To develop a novel positive MRI contrast agent with low toxicity and high sensitivity, ultrasmall MnO nanoparticles were PEGylated via catechol-Mn chelation and conjugated with cRGD as active targeting function to tumor. Particularly, the MnO nanoparticles with a size of ca. 5nm were modified by α,β-poly(aspartic acid)-based graft polymer containing PEG and DOPA moieties and, meanwhile, conjugated with cRGD to produce the contrast agent with a size of ca. 100nm and a longitudinal relaxivity (r1) of 10.2mM(-1)S(-1). Such nanoscaled contrast agent integrated passive- and active-targeting function to tumor, and its efficient accumulation behavior in tumor was verified by in vivo distribution study. At the same time, the PEG moiety played a role of hydrophilic coating to improve the biocompatibility and stability under storing and physiological conditions, and especially might guarantee enough circulation time in blood. Moreover, in vivo MRI revealed a good and long-term effect of enhancing MRI signal for as-fabricated contrast agent while cell viability assay proved its acceptable cytotoxicity for MRI application. On the whole, the as-fabricated PEGylated and cRGD-functionalized contrast agent based on ultrasmall MnO nanoparticles showed a great potential to the T1-weighted MRI diagnosis of tumor.
authors.affiliation: Department of Radiology, University of Minnesota, 420 Delaware St SE, Minneapolis, MN 55455, United States.
authors.forename: Haitao
authors.initials: H
authors.lastname: Huang
authors.affiliation: Modern Testing Services Co., Ltd., No. 105 Guangzhong Rd., Shanghai 201108, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yue
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Radiology, University of Minnesota, 420 Delaware St SE, Minneapolis, MN 55455, United States.
authors.forename: Jafar
authors.initials: J
authors.lastname: Golzarian
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China. Electronic address: jhyu@sist.ecnu.edu.cn.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Yu
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China; College of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070, China. Electronic address: huangjin@iccas.ac.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D001704:Biopolymers / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D017895:Manganese Compounds / Q000737:chemistry*; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D008956:Models, Chemical; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D010087:Oxides / Q000737:chemistry*; D010316:Particle Size; D010456:Peptides, Cyclic / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011859:Radiography; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D001704:Biopolymers; D003287:Contrast Media; D017895:Manganese Compounds; D010087:Oxides; D010456:Peptides, Cyclic; C499773:alpha,beta-poly(aspartic acid); C507169:cyclic arginine-glycine-aspartic acid peptide; D001224:Aspartic Acid; D011092:Polyethylene Glycols; C027424:manganese oxide
keywords: Longitudinal relaxivity; Magnetic resonance imaging; Positive contrast agent; Ultrasmall MnO nanoparticles; cRGD