Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer

Kangan Li,1,4,5,* Shihui Wen,2,* Andrew C Larson,4,5 Mingwu Shen,2 Zhuoli Zhang,4,5 Qian Chen,3 Xiangyang Shi,2,3 Guixiang Zhang1 1Department of Radiology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Co...

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Autores principales:	Li K, Wen S, Larson AC, Shen M, Zhang Z, Chen Q, Shi X, Zhang G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f11d7f3987c6416bb3353ffecee1d1e2
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spelling	oai:doaj.org-article:f11d7f3987c6416bb3353ffecee1d1e22021-12-02T01:07:54ZMultifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer1176-91141178-2013https://doaj.org/article/f11d7f3987c6416bb3353ffecee1d1e22013-07-01T00:00:00Zhttp://www.dovepress.com/multifunctional-dendrimer-based-nanoparticles-for-in-vivo-mrct-dual-mo-a13718https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Kangan Li,1,4,5,* Shihui Wen,2,* Andrew C Larson,4,5 Mingwu Shen,2 Zhuoli Zhang,4,5 Qian Chen,3 Xiangyang Shi,2,3 Guixiang Zhang1 1Department of Radiology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 3State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, People’s Republic of China; 4Departments of Radiology and Biomedical Engineering, Northwestern University, Chicago, IL, USA; 5Robert H Lurie Comprehensive Cancer Center, Chicago, IL, USA *These authors contributed equally to this work Abstract: Development of dual-mode or multi-mode imaging contrast agents is important for accurate and self-confirmatory diagnosis of cancer. We report a new multifunctional, dendrimer-based gold nanoparticle (AuNP) as a dual-modality contrast agent for magnetic resonance (MR)/computed tomography (CT) imaging of breast cancer cells in vitro and in vivo. In this study, amine-terminated generation 5 poly(amidoamine) dendrimers modified with gadolinium chelate (DOTA-NHS) and polyethylene glycol monomethyl ether were used as templates to synthesize AuNPs, followed by Gd(III) chelation and acetylation of the remaining dendrimer terminal amine groups; multifunctional dendrimer-entrapped AuNPs (Gd-Au DENPs) were formed. The formed Gd-Au DENPs were used for both in vitro and in vivo MR/CT imaging of human MCF-7 cancer cells. Both MR and CT images demonstrate that MCF-7 cells and the xenograft tumor model can be effectively imaged. The Gd-Au DENPs uptake, mainly in the cell cytoplasm, was confirmed by transmission electron microscopy. The cell cytotoxicity assay, cell morphology observation, and flow cytometry show that the developed Gd-Au DENPs have good biocompatibility in the given concentration range. Our results clearly suggest that the synthetic Gd-Au DENPs are amenable for dual-modality MR/CT imaging of breast cancer cells. Keywords: PAMAM dendrimers, gold nanoparticles, gadolinium, PEGylation, CT imaging, MR imaging, breast cancer cellsLi KWen SLarson ACShen MZhang ZChen QShi XZhang GDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 2589-2600 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Li K Wen S Larson AC Shen M Zhang Z Chen Q Shi X Zhang G Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer
description	Kangan Li,1,4,5,* Shihui Wen,2,* Andrew C Larson,4,5 Mingwu Shen,2 Zhuoli Zhang,4,5 Qian Chen,3 Xiangyang Shi,2,3 Guixiang Zhang1 1Department of Radiology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 3State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, People’s Republic of China; 4Departments of Radiology and Biomedical Engineering, Northwestern University, Chicago, IL, USA; 5Robert H Lurie Comprehensive Cancer Center, Chicago, IL, USA *These authors contributed equally to this work Abstract: Development of dual-mode or multi-mode imaging contrast agents is important for accurate and self-confirmatory diagnosis of cancer. We report a new multifunctional, dendrimer-based gold nanoparticle (AuNP) as a dual-modality contrast agent for magnetic resonance (MR)/computed tomography (CT) imaging of breast cancer cells in vitro and in vivo. In this study, amine-terminated generation 5 poly(amidoamine) dendrimers modified with gadolinium chelate (DOTA-NHS) and polyethylene glycol monomethyl ether were used as templates to synthesize AuNPs, followed by Gd(III) chelation and acetylation of the remaining dendrimer terminal amine groups; multifunctional dendrimer-entrapped AuNPs (Gd-Au DENPs) were formed. The formed Gd-Au DENPs were used for both in vitro and in vivo MR/CT imaging of human MCF-7 cancer cells. Both MR and CT images demonstrate that MCF-7 cells and the xenograft tumor model can be effectively imaged. The Gd-Au DENPs uptake, mainly in the cell cytoplasm, was confirmed by transmission electron microscopy. The cell cytotoxicity assay, cell morphology observation, and flow cytometry show that the developed Gd-Au DENPs have good biocompatibility in the given concentration range. Our results clearly suggest that the synthetic Gd-Au DENPs are amenable for dual-modality MR/CT imaging of breast cancer cells. Keywords: PAMAM dendrimers, gold nanoparticles, gadolinium, PEGylation, CT imaging, MR imaging, breast cancer cells
format	article
author	Li K Wen S Larson AC Shen M Zhang Z Chen Q Shi X Zhang G
author_facet	Li K Wen S Larson AC Shen M Zhang Z Chen Q Shi X Zhang G
author_sort	Li K
title	Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer
title_short	Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer
title_full	Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer
title_fullStr	Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer
title_full_unstemmed	Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer
title_sort	multifunctional dendrimer-based nanoparticles for in vivo mr/ct dual-modal molecular imaging of breast cancer
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/f11d7f3987c6416bb3353ffecee1d1e2
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Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer

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