High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging
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,...
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Dove Medical Press
2015
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oai:doaj.org-article:6480c34856244e979e2b7814e44ca27b2021-12-02T05:00:34ZHigh molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging1178-2013https://doaj.org/article/6480c34856244e979e2b7814e44ca27b2015-02-01T00:00:00Zhttp://www.dovepress.com/high-molecular-weight-chitosan-derivative-polymeric-micelles-encapsula-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 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 chitosanXiao YLin ZTChen YWang HDeng YLLe DEBin JLi MLiao YLiu YJiang GBBin JDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 1155-1172 (2015) |
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Medicine (General) R5-920 Xiao Y Lin ZT Chen Y Wang H Deng YL Le DE Bin J Li M Liao Y Liu Y Jiang GB Bin J High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging |
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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 |
format |
article |
author |
Xiao Y Lin ZT Chen Y Wang H Deng YL Le DE Bin J Li M Liao Y Liu Y Jiang GB Bin J |
author_facet |
Xiao Y Lin ZT Chen Y Wang H Deng YL Le DE Bin J Li M Liao Y Liu Y Jiang GB Bin J |
author_sort |
Xiao Y |
title |
High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging |
title_short |
High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging |
title_full |
High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging |
title_fullStr |
High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging |
title_full_unstemmed |
High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging |
title_sort |
high molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging |
publisher |
Dove Medical Press |
publishDate |
2015 |
url |
https://doaj.org/article/6480c34856244e979e2b7814e44ca27b |
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