GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells

Ling Wang,1 Yanli An,2 Chenyan Yuan,3 Hao Zhang,2 Chen Liang,2 Fengan Ding,2 Qi Gao,1 Dongsheng Zhang4 1Department of Ultrasonography, Zhong Da Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China; 2Medical School, Southeast University, Nanjing, People&...

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Autores principales:	Wang L, An Y, Yuan C, Zhang H, Liang C, Ding F, Gao Q, Zhang D
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/38bb9f7fa1e34a60a185df29a6bc51be
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spelling	oai:doaj.org-article:38bb9f7fa1e34a60a185df29a6bc51be2021-12-02T07:43:10ZGEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells1178-2013https://doaj.org/article/38bb9f7fa1e34a60a185df29a6bc51be2015-03-01T00:00:00Zhttp://www.dovepress.com/gem-loaded-magnetic-albumin-nanospheres-modified-with-cetuximab-for-si-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Ling Wang,1 Yanli An,2 Chenyan Yuan,3 Hao Zhang,2 Chen Liang,2 Fengan Ding,2 Qi Gao,1 Dongsheng Zhang4 1Department of Ultrasonography, Zhong Da Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China; 2Medical School, Southeast University, Nanjing, People’s Republic of China; 3Department of Clinical Laboratory, Zhong Da Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China; 4Jiangsu Key Laboratory for Biomaterials and Devices, Medical School, Southeast University, Nanjing, People’s Republic of China Background: Targeted delivery is a promising strategy to improve the diagnostic imaging and therapeutic effect of cancers. In this paper, novel cetuximab (C225)-conjugated, gemcitabine (GEM)-containing magnetic albumin nanospheres (C225-GEM/MANs) were fabricated and applied as a theranostic nanocarrier to conduct simultaneous targeting, magnetic resonance imaging (MRI), and double-targeted thermochemotherapy against pancreatic cancer cells. Methods: Fe3O4 nanoparticles (NPs) and GEM co-loaded albumin nanospheres (GEM/MANs) were prepared, and then C225 was further conjugated to synthesize C225-GEM/MANs. Their morphology, mean particle size, GEM encapsulation ratio, specific cell-binding ability, and thermal dynamic profiles were characterized. The effects of discriminating different EGFR-expressing pancreatic cancer cells (AsPC-1 and MIA PaCa-2) and monitoring cellular targeting effects were assessed by targeted MRI. Lastly, the antitumor efficiency of double/C225/magnetic-targeted and nontargeted thermochemotherapy was compared with chemotherapy alone using 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry (FCM) assay. Results: When treated with targeted nanospheres, AsPC-1 cells showed a significantly less intense MRI T2 signal than MIA PaCa-2 cells, while both cells had similar signal strength when incubated with nontargeted nanospheres. T2 signal intensity was significantly lower when magnetic and C225 targeting were combined, rather than used alone. The inhibitory and apoptotic rates of each thermochemotherapy group were significantly higher than those of the chemotherapy-alone groups. Additionally, both MTT and FCM analysis verified that double-targeted thermochemotherapy had the highest targeted killing efficiency among all groups. Conclusion: The C225-GEM/MANs can distinguish various EGFR-expressing live pancreatic cancer cells, monitor diverse cellular targeting effects using targeted MRI imaging, and efficiently mediate double-targeted thermochemotherapy against pancreatic cancer cells. Keywords: gemcitabine, Fe3O4 nanoparticles, theranostic nanocarrierWang LAn YYuan CZhang HLiang CDing FGao QZhang DDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 2507-2519 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Wang L An Y Yuan C Zhang H Liang C Ding F Gao Q Zhang D GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells
description	Ling Wang,1 Yanli An,2 Chenyan Yuan,3 Hao Zhang,2 Chen Liang,2 Fengan Ding,2 Qi Gao,1 Dongsheng Zhang4 1Department of Ultrasonography, Zhong Da Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China; 2Medical School, Southeast University, Nanjing, People’s Republic of China; 3Department of Clinical Laboratory, Zhong Da Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China; 4Jiangsu Key Laboratory for Biomaterials and Devices, Medical School, Southeast University, Nanjing, People’s Republic of China Background: Targeted delivery is a promising strategy to improve the diagnostic imaging and therapeutic effect of cancers. In this paper, novel cetuximab (C225)-conjugated, gemcitabine (GEM)-containing magnetic albumin nanospheres (C225-GEM/MANs) were fabricated and applied as a theranostic nanocarrier to conduct simultaneous targeting, magnetic resonance imaging (MRI), and double-targeted thermochemotherapy against pancreatic cancer cells. Methods: Fe3O4 nanoparticles (NPs) and GEM co-loaded albumin nanospheres (GEM/MANs) were prepared, and then C225 was further conjugated to synthesize C225-GEM/MANs. Their morphology, mean particle size, GEM encapsulation ratio, specific cell-binding ability, and thermal dynamic profiles were characterized. The effects of discriminating different EGFR-expressing pancreatic cancer cells (AsPC-1 and MIA PaCa-2) and monitoring cellular targeting effects were assessed by targeted MRI. Lastly, the antitumor efficiency of double/C225/magnetic-targeted and nontargeted thermochemotherapy was compared with chemotherapy alone using 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry (FCM) assay. Results: When treated with targeted nanospheres, AsPC-1 cells showed a significantly less intense MRI T2 signal than MIA PaCa-2 cells, while both cells had similar signal strength when incubated with nontargeted nanospheres. T2 signal intensity was significantly lower when magnetic and C225 targeting were combined, rather than used alone. The inhibitory and apoptotic rates of each thermochemotherapy group were significantly higher than those of the chemotherapy-alone groups. Additionally, both MTT and FCM analysis verified that double-targeted thermochemotherapy had the highest targeted killing efficiency among all groups. Conclusion: The C225-GEM/MANs can distinguish various EGFR-expressing live pancreatic cancer cells, monitor diverse cellular targeting effects using targeted MRI imaging, and efficiently mediate double-targeted thermochemotherapy against pancreatic cancer cells. Keywords: gemcitabine, Fe3O4 nanoparticles, theranostic nanocarrier
format	article
author	Wang L An Y Yuan C Zhang H Liang C Ding F Gao Q Zhang D
author_facet	Wang L An Y Yuan C Zhang H Liang C Ding F Gao Q Zhang D
author_sort	Wang L
title	GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells
title_short	GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells
title_full	GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells
title_fullStr	GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells
title_full_unstemmed	GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells
title_sort	gem-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/38bb9f7fa1e34a60a185df29a6bc51be
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GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells

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