title: Facile synthesis and functionalization of manganese oxide nanoparticles for targeted T1-weighted tumor MR imaging.
abstract: We report the polyethyleneimine (PEI)-enabled synthesis and functionalization of manganese oxide (Mn3O4) nanoparticles (NPs) for targeted tumor magnetic resonance (MR) imaging in vivo. In this work, monodispersed PEI-coated Mn3O4 NPs were formed by decomposition of acetylacetone manganese via a solvothermal approach. The Mn3O4 NPs with PEI coating were sequentially conjugated with fluorescein isothiocyanate, folic acid (FA)-linked polyethylene glycol (PEG), and PEG monomethyl ether. Followed by final acetylation of the remaining PEI surface amines, multifunctional Mn3O4 NPs were formed and well characterized. We show that the formed multifunctional Mn3O4 NPs with a mean diameter of 8.0 nm possess good water-dispersibility, colloidal stability, and cytocompatibility and hemocompatibility in the given concentration range. Flow cytometry and confocal microscopic observation reveal that the multifunctional Mn3O4 NPs are able to target FA receptor-overexpressing cancer cells in vitro. Importantly, the FA-targeted Mn3O4 NPs can be used as a nanoprobe for efficient T1-weighted MR imaging of cancer cells in vitro and the xenografted tumor model in vivo via an active FA-mediated targeting pathway. With the facile PEI-enabled formation and functionalization, the developed PEI-coated Mn3O4 NPs may be modified with other biomolecules for different biomedical imaging applications.
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Radiology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
authors.forename: Jingchao
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, People's Republic of China.
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Radiology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China. Electronic address: guixinagzhang@sina.com.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, People's Republic of China. Electronic address: xshi@dhu.edu.cn.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. Electronic address: mingwu_shen@yahoo.com.
authors.forename: Mingwu
authors.initials: M
authors.lastname: Shen
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D017895:Manganese Compounds / Q000737:chemistry*; D053768:Metal Nanoparticles; D046529:Microscopy, Electron, Transmission; D009369:Neoplasms / Q000473:pathology*; D010087:Oxides / Q000737:chemistry*
chemical_list: D017895:Manganese Compounds; D010087:Oxides; C027424:manganese oxide
keywords: Folic acid targeting; MR imaging; Manganese oxide nanoparticles; Polyethyleneimine; Tumors