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

Purpose: 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.
Competing Interests: Mr Christopher O McGovern reports a patent “DNA Aptamers Targeting the Cholecystokinin B Receptor (CCKBR) for Diagnosis and Treatment of Pancreatic Ductal Adenocarcinoma and other CCKBR-Expressing Lesions“ pending, a patent “Encapsulation and High Loading Efficiency of Phosphorylated Active Prodrug Metabolic Products in Nanoparticles“ pending. Dr Samuel S Linton reports a patent PCT/US2017/013769 pending. Dr James H Adair has patents 8,071,132 and 9,145,244 B2 issued to PendreaBio, Inc. JHA is also a cofounder and CSO of Keystone Nano for PendreaBio, Inc. Dr Gail L Matters reports a patent “Encapsulation and High Loading Efficiency of Phosphorylated Active Prodrug Metabolic Products in Nanoparticles“ pending and a patent “BIOCONJUGATION OF CALCIUMPHOSPHOSILICATE NANOPARTICLES FOR SELECTIVETARGETING OF CELLS IN VIVO” issued. The authors report no other conflicts of interest in this work.
(© 2021 Abraham et al.)