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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