Gold Nanostars: A Novel Platform for Developing 211At-Labeled Agents for Targeted Alpha-Particle Therapy

Yang Liu,1 Zhengyuan Zhou,2 Yutian Feng,2 Xiao-Guang Zhao,2 Ganesan Vaidyanathan,2 Michael R Zalutsky,1,2 Tuan Vo-Dinh1,3,4 1Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA; 2Department of Radiology, Duke University Medical Center, Durham, NC, 27710, USA; 3Department of...

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Autores principales:	Liu Y, Zhou Z, Feng Y, Zhao XG, Vaidyanathan G, Zalutsky MR, Vo-Dinh T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	astatine-211 (211at) gold nanostars (gns) cancer therapy targeted alpha-particle therapy (tat) Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5d2911eaef9b4861bfe2d09d6ac7c17e
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spelling	oai:doaj.org-article:5d2911eaef9b4861bfe2d09d6ac7c17e2021-12-02T17:51:37ZGold Nanostars: A Novel Platform for Developing 211At-Labeled Agents for Targeted Alpha-Particle Therapy1178-2013https://doaj.org/article/5d2911eaef9b4861bfe2d09d6ac7c17e2021-10-01T00:00:00Zhttps://www.dovepress.com/gold-nanostars-a-novel-platform-for-developing-211at-labeled-agents-fo-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Yang Liu,1 Zhengyuan Zhou,2 Yutian Feng,2 Xiao-Guang Zhao,2 Ganesan Vaidyanathan,2 Michael R Zalutsky,1,2 Tuan Vo-Dinh1,3,4 1Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA; 2Department of Radiology, Duke University Medical Center, Durham, NC, 27710, USA; 3Department of Chemistry, Duke University, Durham, NC, 27708, USA; 4Fitzpatrick Institute for Photonics, Duke University, Durham, NC, 27708, USACorrespondence: Michael R ZalutskyDepartment of Radiology, Duke University Medical Center, 311 Research Drive, 161H Bryan Research Building, Durham, NC, 27710, USAEmail michael.zalutsky@duke.eduTuan Vo-DinhDepartment of Biomedical Engineering, Duke University, 1427 CIEMAS, Box 90281, Durham, NC, 27708, USATel +1 919 660-8520Email tuan.vodinh@duke.eduAim: To develop an innovative 211At nanoplatform with high radiolabeling efficiency and low in vivo deastatination for future targeted alpha-particle therapy (TAT) to treat cancer.Methods: Star-shaped gold nanoparticles, gold nanostars (GNS), were used as the platform for 211At radiolabeling. Radiolabeling efficiency under different reaction conditions was tested. Uptake in the thyroid and stomach after systemic administration was used to evaluate the in vivo stability of 211At-labeled GNS. A subcutaneous U87MG human glioma xenograft murine model was used to preliminarily evaluate the therapeutic efficacy of 211At-labeled GNS after intratumoral administration.Results: The efficiency of labeling GNS with 211At was almost 100% using a simple and rapid synthesis process that was completed in only 1 min. In vitro stability test in serum showed that more than 99% of the 211At activity remained on the GNS after 24 h incubation at 37°C. In vivo biodistribution results showed low uptake in the thyroid (0.44– 0.64%ID) and stomach (0.21– 0.49%ID) between 0.5 and 21 h after intravenous injection, thus indicating excellent in vivo stability of 211At-labeled GNS. The preliminary therapeutic efficacy study demonstrated that 211At labeled GNS substantially reduced tumor growth (P < 0.001; two-way ANOVA) after intratumoral administration.Conclusion: The new 211At radiolabeling strategy based on GNS has the advantages of a simple process, high labeling efficiency, and minimal in vivo dissociation, making it an attractive potential platform for developing TAT agents that warrants further evaluation in future preclinical studies directed to evaluating prospects for clinical translation.Keywords: astatine-211, 211At, gold nanostars, GNS, cancer therapy, targeted alpha-particle therapy, TATLiu YZhou ZFeng YZhao XGVaidyanathan GZalutsky MRVo-Dinh TDove Medical Pressarticleastatine-211 (211at)gold nanostars (gns)cancer therapytargeted alpha-particle therapy (tat)Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 7297-7305 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	astatine-211 (211at) gold nanostars (gns) cancer therapy targeted alpha-particle therapy (tat) Medicine (General) R5-920
spellingShingle	astatine-211 (211at) gold nanostars (gns) cancer therapy targeted alpha-particle therapy (tat) Medicine (General) R5-920 Liu Y Zhou Z Feng Y Zhao XG Vaidyanathan G Zalutsky MR Vo-Dinh T Gold Nanostars: A Novel Platform for Developing 211At-Labeled Agents for Targeted Alpha-Particle Therapy
description	Yang Liu,1 Zhengyuan Zhou,2 Yutian Feng,2 Xiao-Guang Zhao,2 Ganesan Vaidyanathan,2 Michael R Zalutsky,1,2 Tuan Vo-Dinh1,3,4 1Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA; 2Department of Radiology, Duke University Medical Center, Durham, NC, 27710, USA; 3Department of Chemistry, Duke University, Durham, NC, 27708, USA; 4Fitzpatrick Institute for Photonics, Duke University, Durham, NC, 27708, USACorrespondence: Michael R ZalutskyDepartment of Radiology, Duke University Medical Center, 311 Research Drive, 161H Bryan Research Building, Durham, NC, 27710, USAEmail michael.zalutsky@duke.eduTuan Vo-DinhDepartment of Biomedical Engineering, Duke University, 1427 CIEMAS, Box 90281, Durham, NC, 27708, USATel +1 919 660-8520Email tuan.vodinh@duke.eduAim: To develop an innovative 211At nanoplatform with high radiolabeling efficiency and low in vivo deastatination for future targeted alpha-particle therapy (TAT) to treat cancer.Methods: Star-shaped gold nanoparticles, gold nanostars (GNS), were used as the platform for 211At radiolabeling. Radiolabeling efficiency under different reaction conditions was tested. Uptake in the thyroid and stomach after systemic administration was used to evaluate the in vivo stability of 211At-labeled GNS. A subcutaneous U87MG human glioma xenograft murine model was used to preliminarily evaluate the therapeutic efficacy of 211At-labeled GNS after intratumoral administration.Results: The efficiency of labeling GNS with 211At was almost 100% using a simple and rapid synthesis process that was completed in only 1 min. In vitro stability test in serum showed that more than 99% of the 211At activity remained on the GNS after 24 h incubation at 37°C. In vivo biodistribution results showed low uptake in the thyroid (0.44– 0.64%ID) and stomach (0.21– 0.49%ID) between 0.5 and 21 h after intravenous injection, thus indicating excellent in vivo stability of 211At-labeled GNS. The preliminary therapeutic efficacy study demonstrated that 211At labeled GNS substantially reduced tumor growth (P < 0.001; two-way ANOVA) after intratumoral administration.Conclusion: The new 211At radiolabeling strategy based on GNS has the advantages of a simple process, high labeling efficiency, and minimal in vivo dissociation, making it an attractive potential platform for developing TAT agents that warrants further evaluation in future preclinical studies directed to evaluating prospects for clinical translation.Keywords: astatine-211, 211At, gold nanostars, GNS, cancer therapy, targeted alpha-particle therapy, TAT
format	article
author	Liu Y Zhou Z Feng Y Zhao XG Vaidyanathan G Zalutsky MR Vo-Dinh T
author_facet	Liu Y Zhou Z Feng Y Zhao XG Vaidyanathan G Zalutsky MR Vo-Dinh T
author_sort	Liu Y
title	Gold Nanostars: A Novel Platform for Developing 211At-Labeled Agents for Targeted Alpha-Particle Therapy
title_short	Gold Nanostars: A Novel Platform for Developing 211At-Labeled Agents for Targeted Alpha-Particle Therapy
title_full	Gold Nanostars: A Novel Platform for Developing 211At-Labeled Agents for Targeted Alpha-Particle Therapy
title_fullStr	Gold Nanostars: A Novel Platform for Developing 211At-Labeled Agents for Targeted Alpha-Particle Therapy
title_full_unstemmed	Gold Nanostars: A Novel Platform for Developing 211At-Labeled Agents for Targeted Alpha-Particle Therapy
title_sort	gold nanostars: a novel platform for developing 211at-labeled agents for targeted alpha-particle therapy
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/5d2911eaef9b4861bfe2d09d6ac7c17e
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Gold Nanostars: A Novel Platform for Developing 211At-Labeled Agents for Targeted Alpha-Particle Therapy

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