Toxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice

You-Wei Wang, Kai Yang, Hong Tang, Dan Chen, Yun-Long Bai Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: Nanotechnology-based near-infrared quantum dots (NIR QDs) have many e...

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Autores principales: Wang YW, Yang K, Tang H, Chen D, Bai YL
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Publicado: Dove Medical Press 2014
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spelling oai:doaj.org-article:cbfbf59485ca42e5ae1d5722dc9cd9812021-12-02T02:04:16ZToxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice1178-2013https://doaj.org/article/cbfbf59485ca42e5ae1d5722dc9cd9812014-10-01T00:00:00Zhttp://www.dovepress.com/toxicity-assessment-of-repeated-intravenous-injections-of-argininendas-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 You-Wei Wang, Kai Yang, Hong Tang, Dan Chen, Yun-Long Bai Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: Nanotechnology-based near-infrared quantum dots (NIR QDs) have many excellent optical properties, such as high fluorescence intensity, good fluorescence stability, and strong tissue-penetrating ability. Integrin αvß3 is highly and specifically expressed in tumor angiogenic vessel endothelial cells of almost all carcinomas. Recent studies have shown that NIR QDs linked to peptides containing the arginine–glycine–aspartic acid (RGD) sequence (NIR QDs-RGD) can specifically target integrin αvß3 expressed in endothelial cells of tumor angiogenic vessels in vivo, and they offer great potential for early cancer diagnosis, in vivo tumor imaging, and tumor individualized therapy. However, the toxicity profile of NIR QDs-RGD has not been reported. This study was conducted to investigate the toxicity of NIR QDs-RGD when intravenously administered to mice singly and repeatedly at the dose required for successful tumor imaging in vivo.Materials and methods: A NIR QDs-RGD probe was prepared by linking NIR QDs with the maximum emission wavelength of 800 nm (QD800) to the RGD peptide (QD800-RGD). QD800-RGD was intravenously injected to BALB/C mice once or twice (200 pmol equivalent of QD800 for each injection). phosphate-buffered saline solution was used as control. Fourteen days postinjection, toxicity tests were performed, including complete blood count (white blood cell, red blood cell, hemoglobin, platelets, lymphocytes, and neutrophils) and serum biochemical analysis (total protein, albumin, albumin/globulin, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen). The coefficients of liver, spleen, kidney, and lung weight to body weight were measured, as well as their oxidation and antioxidation indicators, including superoxide dismutase, glutathione, and malondialdehyde. The organs were also examined histopathologically.Results: After one or two intravenous injections of QD800-RGD, as compared with control, no significant differences were observed in the complete blood count; biochemical indicators of blood serum, organ coefficient, and oxidation and antioxidation indicators; and no cell necrosis or inflammation were seen in the liver, spleen, kidney, or lung through histopathological examination.Conclusion: Our data demonstrate that the single and repeated intravenous injection of QD800-RGD at a dose needed for successful tumor imaging in vivo is not toxic to mice. Our work lays a solid foundation for further biomedical applications of NIR QDs-RGD. Keywords: nanotechnology, RGD peptides, integrin αvß3, quantum dots, intravenous injection, toxicity Wang YWYang KTang HChen DBai YLDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 4809-4817 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Wang YW
Yang K
Tang H
Chen D
Bai YL
Toxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice
description You-Wei Wang, Kai Yang, Hong Tang, Dan Chen, Yun-Long Bai Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: Nanotechnology-based near-infrared quantum dots (NIR QDs) have many excellent optical properties, such as high fluorescence intensity, good fluorescence stability, and strong tissue-penetrating ability. Integrin αvß3 is highly and specifically expressed in tumor angiogenic vessel endothelial cells of almost all carcinomas. Recent studies have shown that NIR QDs linked to peptides containing the arginine–glycine–aspartic acid (RGD) sequence (NIR QDs-RGD) can specifically target integrin αvß3 expressed in endothelial cells of tumor angiogenic vessels in vivo, and they offer great potential for early cancer diagnosis, in vivo tumor imaging, and tumor individualized therapy. However, the toxicity profile of NIR QDs-RGD has not been reported. This study was conducted to investigate the toxicity of NIR QDs-RGD when intravenously administered to mice singly and repeatedly at the dose required for successful tumor imaging in vivo.Materials and methods: A NIR QDs-RGD probe was prepared by linking NIR QDs with the maximum emission wavelength of 800 nm (QD800) to the RGD peptide (QD800-RGD). QD800-RGD was intravenously injected to BALB/C mice once or twice (200 pmol equivalent of QD800 for each injection). phosphate-buffered saline solution was used as control. Fourteen days postinjection, toxicity tests were performed, including complete blood count (white blood cell, red blood cell, hemoglobin, platelets, lymphocytes, and neutrophils) and serum biochemical analysis (total protein, albumin, albumin/globulin, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen). The coefficients of liver, spleen, kidney, and lung weight to body weight were measured, as well as their oxidation and antioxidation indicators, including superoxide dismutase, glutathione, and malondialdehyde. The organs were also examined histopathologically.Results: After one or two intravenous injections of QD800-RGD, as compared with control, no significant differences were observed in the complete blood count; biochemical indicators of blood serum, organ coefficient, and oxidation and antioxidation indicators; and no cell necrosis or inflammation were seen in the liver, spleen, kidney, or lung through histopathological examination.Conclusion: Our data demonstrate that the single and repeated intravenous injection of QD800-RGD at a dose needed for successful tumor imaging in vivo is not toxic to mice. Our work lays a solid foundation for further biomedical applications of NIR QDs-RGD. Keywords: nanotechnology, RGD peptides, integrin αvß3, quantum dots, intravenous injection, toxicity 
format article
author Wang YW
Yang K
Tang H
Chen D
Bai YL
author_facet Wang YW
Yang K
Tang H
Chen D
Bai YL
author_sort Wang YW
title Toxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice
title_short Toxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice
title_full Toxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice
title_fullStr Toxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice
title_full_unstemmed Toxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice
title_sort toxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated cdsete/zns quantum dots in mice
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/cbfbf59485ca42e5ae1d5722dc9cd981
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