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Aptamer-Targeted Calcium Phosphosilicate Nanoparticles for Effective Imaging of Pancreatic and Prostate Cancer
- Source :
- International Journal of Nanomedicine
- Publication Year :
- 2021
- Publisher :
- Dove Press, 2021.
-
Abstract
- 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
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 11782013
- Database :
- OpenAIRE
- Journal :
- International Journal of Nanomedicine
- Accession number :
- edsair.doi.dedup.....4e5bdb4292a8def3e2f3599934b7d779