Doxorubicin and indocyanine green loaded superparamagnetic iron oxide nanoparticles with PEGylated phospholipid coating for magnetic resonance with fluorescence imaging and chemotherapy of glioma

Chen Shen,1,2,* Xiaoxiong Wang,1,2,* Zhixing Zheng,1,2,* Chuang Gao,3 Xin Chen,1,2 Shiguang Zhao,1,2 Zhifei Dai3 1Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China; 2Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin...

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Autores principales: Shen C, Wang X, Zheng Z, Gao C, Chen X, Zhao S, Dai Z
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Publicado: Dove Medical Press 2018
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spelling oai:doaj.org-article:70678126a88646789d2d88e994b0af0a2021-12-02T05:19:57ZDoxorubicin and indocyanine green loaded superparamagnetic iron oxide nanoparticles with PEGylated phospholipid coating for magnetic resonance with fluorescence imaging and chemotherapy of glioma1178-2013https://doaj.org/article/70678126a88646789d2d88e994b0af0a2018-12-01T00:00:00Zhttps://www.dovepress.com/doxorubicin-and-indocyanine-green-loaded-superparamagnetic-iron-oxide--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Chen Shen,1,2,* Xiaoxiong Wang,1,2,* Zhixing Zheng,1,2,* Chuang Gao,3 Xin Chen,1,2 Shiguang Zhao,1,2 Zhifei Dai3 1Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China; 2Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, Heilongjiang, China; 3Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China *These authors contributed equally to this work Background: Glioma represents the most common malignant brain tumor. Outcomes of surgical resection are often unsatisfactory due to low sensitivity or resolution of imaging methods. Moreover, the use of traditional chemotherapeutics, such as doxorubicin (DOX), is limited due to their low blood–brain barrier (BBB) permeability. Recently, the development of nanotechnology could overcome these obstacles. Materials and methods: Hydrophobic superparamagnetic iron oxide nanoparticles (SPIO NPs) were prepared with the use of thermal decomposition method. They were coated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG 2000) and DOX using a thin-film hydration method followed by loading of indocyanine green (ICG) into the phospholipid layers. Details regarding the characteristics of NPs were determined. The in vitro biocompatibility and antitumor efficacy were established with the use of MTT assay. In vivo fluorescence and magnetic resonance (MR) imaging were used to evaluate BBB penetration and accumulation of NPs at the tumor site. Antitumor efficacy was evaluated using measures of tumor size, median survival times, body weights, and H&E staining. Results: The multifunctional NPs generated had an average diameter of 22.9 nm, a zeta potential of -38.19 mV, and were capable of providing a sustained release of DOX. In vitro experiments demonstrated that the SPIO@DSPE-PEG/DOX/ICG NPs effectively enhanced cellular uptake of DOX as compared with that of free DOX. In vivo fluorescence and MR imaging revealed that the NPs not only effectively crossed the BBB but selectively accumulated at the tumor site. Meanwhile, among all groups studied, C6 glioma-bearing rats treated with the NPs exhibited the maximal degree of therapeutic efficacy, including smallest tumor volume, lowest body weight loss, and longest survival times, with no obvious side effects. Conclusion: These results suggest that the SPIO@DSPE-PEG/DOX/ICG NPs can not only function as a nanoprobe for MR and fluorescence bimodal imaging, but also as a vehicle to deliver chemotherapeutic drugs to the tumor site, to achieve the theranostic treatment of glioma. Keywords: SPIO NPs, BBB, MR imaging, fluorescence imaging, chemotherapyShen CWang XZheng ZGao CChen XZhao SDai ZDove Medical PressarticleSPIO NPsBBBMR imagingfluorescence imagingchemotherapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 101-117 (2018)
institution DOAJ
collection DOAJ
language EN
topic SPIO NPs
BBB
MR imaging
fluorescence imaging
chemotherapy
Medicine (General)
R5-920
spellingShingle SPIO NPs
BBB
MR imaging
fluorescence imaging
chemotherapy
Medicine (General)
R5-920
Shen C
Wang X
Zheng Z
Gao C
Chen X
Zhao S
Dai Z
Doxorubicin and indocyanine green loaded superparamagnetic iron oxide nanoparticles with PEGylated phospholipid coating for magnetic resonance with fluorescence imaging and chemotherapy of glioma
description Chen Shen,1,2,* Xiaoxiong Wang,1,2,* Zhixing Zheng,1,2,* Chuang Gao,3 Xin Chen,1,2 Shiguang Zhao,1,2 Zhifei Dai3 1Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China; 2Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, Heilongjiang, China; 3Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China *These authors contributed equally to this work Background: Glioma represents the most common malignant brain tumor. Outcomes of surgical resection are often unsatisfactory due to low sensitivity or resolution of imaging methods. Moreover, the use of traditional chemotherapeutics, such as doxorubicin (DOX), is limited due to their low blood–brain barrier (BBB) permeability. Recently, the development of nanotechnology could overcome these obstacles. Materials and methods: Hydrophobic superparamagnetic iron oxide nanoparticles (SPIO NPs) were prepared with the use of thermal decomposition method. They were coated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG 2000) and DOX using a thin-film hydration method followed by loading of indocyanine green (ICG) into the phospholipid layers. Details regarding the characteristics of NPs were determined. The in vitro biocompatibility and antitumor efficacy were established with the use of MTT assay. In vivo fluorescence and magnetic resonance (MR) imaging were used to evaluate BBB penetration and accumulation of NPs at the tumor site. Antitumor efficacy was evaluated using measures of tumor size, median survival times, body weights, and H&E staining. Results: The multifunctional NPs generated had an average diameter of 22.9 nm, a zeta potential of -38.19 mV, and were capable of providing a sustained release of DOX. In vitro experiments demonstrated that the SPIO@DSPE-PEG/DOX/ICG NPs effectively enhanced cellular uptake of DOX as compared with that of free DOX. In vivo fluorescence and MR imaging revealed that the NPs not only effectively crossed the BBB but selectively accumulated at the tumor site. Meanwhile, among all groups studied, C6 glioma-bearing rats treated with the NPs exhibited the maximal degree of therapeutic efficacy, including smallest tumor volume, lowest body weight loss, and longest survival times, with no obvious side effects. Conclusion: These results suggest that the SPIO@DSPE-PEG/DOX/ICG NPs can not only function as a nanoprobe for MR and fluorescence bimodal imaging, but also as a vehicle to deliver chemotherapeutic drugs to the tumor site, to achieve the theranostic treatment of glioma. Keywords: SPIO NPs, BBB, MR imaging, fluorescence imaging, chemotherapy
format article
author Shen C
Wang X
Zheng Z
Gao C
Chen X
Zhao S
Dai Z
author_facet Shen C
Wang X
Zheng Z
Gao C
Chen X
Zhao S
Dai Z
author_sort Shen C
title Doxorubicin and indocyanine green loaded superparamagnetic iron oxide nanoparticles with PEGylated phospholipid coating for magnetic resonance with fluorescence imaging and chemotherapy of glioma
title_short Doxorubicin and indocyanine green loaded superparamagnetic iron oxide nanoparticles with PEGylated phospholipid coating for magnetic resonance with fluorescence imaging and chemotherapy of glioma
title_full Doxorubicin and indocyanine green loaded superparamagnetic iron oxide nanoparticles with PEGylated phospholipid coating for magnetic resonance with fluorescence imaging and chemotherapy of glioma
title_fullStr Doxorubicin and indocyanine green loaded superparamagnetic iron oxide nanoparticles with PEGylated phospholipid coating for magnetic resonance with fluorescence imaging and chemotherapy of glioma
title_full_unstemmed Doxorubicin and indocyanine green loaded superparamagnetic iron oxide nanoparticles with PEGylated phospholipid coating for magnetic resonance with fluorescence imaging and chemotherapy of glioma
title_sort doxorubicin and indocyanine green loaded superparamagnetic iron oxide nanoparticles with pegylated phospholipid coating for magnetic resonance with fluorescence imaging and chemotherapy of glioma
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/70678126a88646789d2d88e994b0af0a
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