Aptamer-Targeted Calcium Phosphosilicate Nanoparticles for Effective Imaging of Pancreatic and Prostate Cancer

Thomas Abraham,1 Christopher O McGovern,2 Samuel S Linton,2 Zachary Wilczynski,3 James H Adair,3,4 Gail L Matters2 1Departments of Neural and Behavioral Sciences and the Microscopy Imaging Core Facility, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA; 2Department of B...

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Autores principales:	Abraham T, McGovern CO, Linton SS, Wilczynski Z, Adair JH, Matters GL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	tumor detection icg nanoparticles aptamer targeting proglumide Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c49de3a6d236487984517533fae18c19
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spelling	oai:doaj.org-article:c49de3a6d236487984517533fae18c192021-12-02T14:25:43ZAptamer-Targeted Calcium Phosphosilicate Nanoparticles for Effective Imaging of Pancreatic and Prostate Cancer1178-2013https://doaj.org/article/c49de3a6d236487984517533fae18c192021-03-01T00:00:00Zhttps://www.dovepress.com/aptamer-targeted-calcium-phosphosilicate-nanoparticles-for-effective-i-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Thomas Abraham,1 Christopher O McGovern,2 Samuel S Linton,2 Zachary Wilczynski,3 James H Adair,3,4 Gail L Matters2 1Departments of Neural and Behavioral Sciences and the Microscopy Imaging Core Facility, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA; 2Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA; 3Departments of Materials Science, The Pennsylvania State University, University Park, PA, 16802, USA; 4Department of Biomedical Engineering and Pharmacology, The Pennsylvania State University, University Park, PA, 16802, USACorrespondence: Gail L MattersDepartment of Biochemistry and Molecular Biology, H171, The Pennsylvania State University College of Medicine, PO Box 850, Hershey, PA, 17033, USATel +1 717 531-4098Fax +1 717 531-7072Email gmatters@pennstatehealth.psu.eduPurpose: Accurate tumor identification and staging can be difficult. Aptamer-targeted indocyanine green (ICG)-nanoparticles can enhance near-infrared fluorescent imaging of pancreatic and prostate tumors and could improve early cancer detection. This project explored whether calcium-phosphosilicate nanoparticles, also known as NanoJackets (NJs), that were bioconjugated with a tumor-specific targeting DNA aptamer could improve the non-invasive detection of pancreatic and prostate tumors.Methods: Using in vivo near-infrared optical imaging and ex vivo fluorescence analysis, DNA aptamer-targeted ICG-loaded NJs were compared to untargeted NJs for detection of tumors.Results: Nanoparticles were bioconjugated with the DNA aptamer AP1153, which binds to the CCK-B receptor (CCKBR). Aptamer bioconjugated NJs were not significantly increased in size compared with unconjugated nanoparticles. AP1153-ICG-NJ accumulation in orthotopic pancreatic tumors peaked at 18 h post-injection and the ICG signal was cleared by 36 h with no evidence on uptake by non-tumor tissues. Ex vivo tumor imaging confirmed the aptamer-targeted NJs accumulated to higher levels than untargeted NJs, were not taken up by normal pancreas, exited from the tumor vasculature, and were well-dispersed throughout pancreatic and prostate tumors despite extensive fibrosis. Specificity for AP1153-NJ binding to the CCK-B receptor on pancreatic tumor cells was confirmed by pre-treating tumor-bearing mice with the CCK receptor antagonist proglumide. Proglumide pre-treatment reduced the in vivo tumoral accumulation of AP1153-NJs to levels comparable to that of untargeted NJs.Conclusion: Through specific interactions with CCK-B receptors, tumor-targeted nanoparticles containing either ICG or rhodamine WT were well distributed throughout the matrix of both pancreatic and prostate tumors. Tumor-targeted NJs carrying various imaging agents can enhance tumor detection.Keywords: tumor detection, ICG nanoparticles, aptamer targeting, proglumideAbraham TMcGovern COLinton SSWilczynski ZAdair JHMatters GLDove Medical Pressarticletumor detectionicg nanoparticlesaptamer targetingproglumideMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 2297-2309 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tumor detection icg nanoparticles aptamer targeting proglumide Medicine (General) R5-920
spellingShingle	tumor detection icg nanoparticles aptamer targeting proglumide Medicine (General) R5-920 Abraham T McGovern CO Linton SS Wilczynski Z Adair JH Matters GL Aptamer-Targeted Calcium Phosphosilicate Nanoparticles for Effective Imaging of Pancreatic and Prostate Cancer
description	Thomas Abraham,1 Christopher O McGovern,2 Samuel S Linton,2 Zachary Wilczynski,3 James H Adair,3,4 Gail L Matters2 1Departments of Neural and Behavioral Sciences and the Microscopy Imaging Core Facility, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA; 2Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA; 3Departments of Materials Science, The Pennsylvania State University, University Park, PA, 16802, USA; 4Department of Biomedical Engineering and Pharmacology, The Pennsylvania State University, University Park, PA, 16802, USACorrespondence: Gail L MattersDepartment of Biochemistry and Molecular Biology, H171, The Pennsylvania State University College of Medicine, PO Box 850, Hershey, PA, 17033, USATel +1 717 531-4098Fax +1 717 531-7072Email gmatters@pennstatehealth.psu.eduPurpose: Accurate tumor identification and staging can be difficult. Aptamer-targeted indocyanine green (ICG)-nanoparticles can enhance near-infrared fluorescent imaging of pancreatic and prostate tumors and could improve early cancer detection. This project explored whether calcium-phosphosilicate nanoparticles, also known as NanoJackets (NJs), that were bioconjugated with a tumor-specific targeting DNA aptamer could improve the non-invasive detection of pancreatic and prostate tumors.Methods: Using in vivo near-infrared optical imaging and ex vivo fluorescence analysis, DNA aptamer-targeted ICG-loaded NJs were compared to untargeted NJs for detection of tumors.Results: Nanoparticles were bioconjugated with the DNA aptamer AP1153, which binds to the CCK-B receptor (CCKBR). Aptamer bioconjugated NJs were not significantly increased in size compared with unconjugated nanoparticles. AP1153-ICG-NJ accumulation in orthotopic pancreatic tumors peaked at 18 h post-injection and the ICG signal was cleared by 36 h with no evidence on uptake by non-tumor tissues. Ex vivo tumor imaging confirmed the aptamer-targeted NJs accumulated to higher levels than untargeted NJs, were not taken up by normal pancreas, exited from the tumor vasculature, and were well-dispersed throughout pancreatic and prostate tumors despite extensive fibrosis. Specificity for AP1153-NJ binding to the CCK-B receptor on pancreatic tumor cells was confirmed by pre-treating tumor-bearing mice with the CCK receptor antagonist proglumide. Proglumide pre-treatment reduced the in vivo tumoral accumulation of AP1153-NJs to levels comparable to that of untargeted NJs.Conclusion: Through specific interactions with CCK-B receptors, tumor-targeted nanoparticles containing either ICG or rhodamine WT were well distributed throughout the matrix of both pancreatic and prostate tumors. Tumor-targeted NJs carrying various imaging agents can enhance tumor detection.Keywords: tumor detection, ICG nanoparticles, aptamer targeting, proglumide
format	article
author	Abraham T McGovern CO Linton SS Wilczynski Z Adair JH Matters GL
author_facet	Abraham T McGovern CO Linton SS Wilczynski Z Adair JH Matters GL
author_sort	Abraham T
title	Aptamer-Targeted Calcium Phosphosilicate Nanoparticles for Effective Imaging of Pancreatic and Prostate Cancer
title_short	Aptamer-Targeted Calcium Phosphosilicate Nanoparticles for Effective Imaging of Pancreatic and Prostate Cancer
title_full	Aptamer-Targeted Calcium Phosphosilicate Nanoparticles for Effective Imaging of Pancreatic and Prostate Cancer
title_fullStr	Aptamer-Targeted Calcium Phosphosilicate Nanoparticles for Effective Imaging of Pancreatic and Prostate Cancer
title_full_unstemmed	Aptamer-Targeted Calcium Phosphosilicate Nanoparticles for Effective Imaging of Pancreatic and Prostate Cancer
title_sort	aptamer-targeted calcium phosphosilicate nanoparticles for effective imaging of pancreatic and prostate cancer
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/c49de3a6d236487984517533fae18c19
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Aptamer-Targeted Calcium Phosphosilicate Nanoparticles for Effective Imaging of Pancreatic and Prostate Cancer

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