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High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging

Authors Xiao Y, Lin ZT, Chen Y, Wang H, Deng YL, Le DE, Bin J, Li M, Liao Y, Liu Y, Jiang GB, Bin J

Received 28 June 2014

Accepted for publication 12 October 2014

Published 5 February 2015 Volume 2015:10(1) Pages 1155—1172

DOI https://doi.org/10.2147/IJN.S70022

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Lei Yang

Yunbin Xiao,1,* Zuan Tao Lin,2,* Yanmei Chen,1 He Wang,1 Ya Li Deng,2 D Elizabeth Le,3 Jianguo Bin,1 Meiyu Li,1 Yulin Liao,1 Yili Liu,1 Gangbiao Jiang,2 Jianping Bin1

1State Key Laboratory of Organ Failure Research, Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Pharmaceutical Engineering, South China Agricultural University, Guangzhou, People’s Republic of China; 3Cardiovascular Division, Oregon Health and Science University, Portland, OR, USA

*These authors contributed equally to this work

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.

Keywords: superparamagnetic iron oxide, magnetic resonance imaging, polymeric micelles, folate receptors, tumor-targeted MRI, N-palmitoyl chitosan


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