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...

Full description

Bibliographic Details
Main Authors: Shen C, Wang X, Zheng Z, Gao C, Chen X, Zhao S, Dai Z
Format: Article
Language:English
Published: Dove Medical Press 2018-12-01
Series:International Journal of Nanomedicine
Subjects:
Online Access:https://www.dovepress.com/doxorubicin-and-indocyanine-green-loaded-superparamagnetic-iron-oxide--peer-reviewed-article-IJN
_version_ 1818345783464820736
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
collection DOAJ
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
first_indexed 2024-12-13T17:07:52Z
format Article
id doaj.art-70678126a88646789d2d88e994b0af0a
institution Directory Open Access Journal
issn 1178-2013
language English
last_indexed 2024-12-13T17:07:52Z
publishDate 2018-12-01
publisher Dove Medical Press
record_format Article
series International Journal of Nanomedicine
spelling doaj.art-70678126a88646789d2d88e994b0af0a2022-12-21T23:37:39ZengDove Medical PressInternational Journal of Nanomedicine1178-20132018-12-01Volume 1410111743187Doxorubicin and indocyanine green loaded superparamagnetic iron oxide nanoparticles with PEGylated phospholipid coating for magnetic resonance with fluorescence imaging and chemotherapy of gliomaShen CWang XZheng ZGao CChen XZhao SDai ZChen 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, chemotherapyhttps://www.dovepress.com/doxorubicin-and-indocyanine-green-loaded-superparamagnetic-iron-oxide--peer-reviewed-article-IJNSPIO NPsBBBMR imagingfluorescence imagingchemotherapy
spellingShingle 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
International Journal of Nanomedicine
SPIO NPs
BBB
MR imaging
fluorescence imaging
chemotherapy
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_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_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_sort doxorubicin and indocyanine green loaded superparamagnetic iron oxide nanoparticles with pegylated phospholipid coating for magnetic resonance with fluorescence imaging and chemotherapy of glioma
topic SPIO NPs
BBB
MR imaging
fluorescence imaging
chemotherapy
url https://www.dovepress.com/doxorubicin-and-indocyanine-green-loaded-superparamagnetic-iron-oxide--peer-reviewed-article-IJN
work_keys_str_mv AT shenc doxorubicinandindocyaninegreenloadedsuperparamagneticironoxidenanoparticleswithpegylatedphospholipidcoatingformagneticresonancewithfluorescenceimagingandchemotherapyofglioma
AT wangx doxorubicinandindocyaninegreenloadedsuperparamagneticironoxidenanoparticleswithpegylatedphospholipidcoatingformagneticresonancewithfluorescenceimagingandchemotherapyofglioma
AT zhengz doxorubicinandindocyaninegreenloadedsuperparamagneticironoxidenanoparticleswithpegylatedphospholipidcoatingformagneticresonancewithfluorescenceimagingandchemotherapyofglioma
AT gaoc doxorubicinandindocyaninegreenloadedsuperparamagneticironoxidenanoparticleswithpegylatedphospholipidcoatingformagneticresonancewithfluorescenceimagingandchemotherapyofglioma
AT chenx doxorubicinandindocyaninegreenloadedsuperparamagneticironoxidenanoparticleswithpegylatedphospholipidcoatingformagneticresonancewithfluorescenceimagingandchemotherapyofglioma
AT zhaos doxorubicinandindocyaninegreenloadedsuperparamagneticironoxidenanoparticleswithpegylatedphospholipidcoatingformagneticresonancewithfluorescenceimagingandchemotherapyofglioma
AT daiz doxorubicinandindocyaninegreenloadedsuperparamagneticironoxidenanoparticleswithpegylatedphospholipidcoatingformagneticresonancewithfluorescenceimagingandchemotherapyofglioma