title: High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging.
abstract: Magnetic resonance imaging (MRI) contrast agents based on chitosan derivatives have great potential for diagnosing diseases. However, stable tumor-targeted MRI contrast agents using micelles prepared from high molecular weight chitosan derivatives are seldom reported. In this study, we developed a novel tumor-targeted MRI vehicle via superparamagnetic iron oxide nanoparticles (SPIONs) encapsulated in self-aggregating polymeric folate-conjugated N-palmitoyl chitosan (FAPLCS) micelles. The tumor-targeting ability of FAPLCS/SPIONs was demonstrated in vitro and in vivo. The results of dynamic light scattering experiments showed that the micelles had a relatively narrow size distribution (136.60±3.90 nm) and excellent stability. FAPLCS/SPIONs showed low cytotoxicity and excellent biocompatibility in cellular toxicity tests. Both in vitro and in vivo studies demonstrated that FAPLCS/SPIONs bound specifically to folate receptor-positive HeLa cells, and that FAPLCS/SPIONs accumulated predominantly in established HeLa-derived tumors in mice. The signal intensities of T2-weighted images in established HeLa-derived tumors were reduced dramatically after intravenous micelle administration. Our study indicates that FAPLCS/SPION micelles can potentially serve as safe and effective MRI contrast agents for detecting tumors that overexpress folate receptors.
authors.affiliation: State Key Laboratory of Organ Failure Research, Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Yunbin
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Pharmaceutical Engineering, South China Agricultural University, Guangzhou, People's Republic of China.
authors.forename: Zuan Tao
authors.initials: ZT
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Organ Failure Research, Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Organ Failure Research, Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Engineering, South China Agricultural University, Guangzhou, People's Republic of China.
authors.forename: Ya Li
authors.initials: YL
authors.lastname: Deng
authors.affiliation: Cardiovascular Division, Oregon Health and Science University, Portland, OR, USA.
authors.forename: D Elizabeth
authors.initials: DE
authors.lastname: Le
authors.affiliation: State Key Laboratory of Organ Failure Research, Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Bin
authors.affiliation: State Key Laboratory of Organ Failure Research, Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Organ Failure Research, Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Organ Failure Research, Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Engineering, South China Agricultural University, Guangzhou, People's Republic of China.
authors.forename: Gangbiao
authors.initials: G
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Organ Failure Research, Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Bin
mesh_terms: D000818:Animals; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics; D005492:Folic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D006367:HeLa Cells; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008823:Micelles; D009369:Neoplasms / Q000473:pathology*
chemical_list: D003287:Contrast Media; D058185:Magnetite Nanoparticles; D008823:Micelles; C510699:N-palmitoyl chitosan; D048271:Chitosan; D005492:Folic Acid
keywords: N-palmitoyl chitosan; folate receptors; magnetic resonance imaging; polymeric micelles; superparamagnetic iron oxide; tumor-targeted MRI