Aptamer-Targeted Calcium Phosphosilicate Nanoparticles for Effective Imaging of Pancreatic and Prostate Cancer
| Autor: | Christopher O. McGovern, James H. Adair, Samuel S. Linton, Thomas Abraham, Zachary R. Wilczynski, Gail L. Matters |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Diagnostic Imaging
Indocyanine Green Male proglumide Infrared Rays Aptamer Biophysics Pharmaceutical Science Bioengineering Fluorescence Biomaterials Prostate cancer chemistry.chemical_compound Mice Pancreatic tumor In vivo International Journal of Nanomedicine Cell Line Tumor Drug Discovery ICG nanoparticles medicine Tumor Microenvironment Animals Humans Receptor Coloring Agents tumor detection Original Research Neovascularization Pathologic Chemistry Rhodamines Silicates Organic Chemistry Prostatic Neoplasms General Medicine Aptamers Nucleotide medicine.disease Pancreatic Neoplasms Cholecystokinin B receptor Cancer research Nanoparticles Calcium Receptors Cholecystokinin aptamer targeting Indocyanine green Ex vivo |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|