Ultra-bright fluorescent nanoparticles for colorectal adenoma detection

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Abstract Colorectal cancer is the 3rd leading cause of cancer-related mortality. Colorectal cancer screening significantly reduces cancer mortality through the detection of precancerous adenomas and removal with colonoscopy polypectomy. Inspection of the colon upon withdrawal from the cecum during colonoscopy is the most common method of adenoma detection in the United States. However, substantial evidence suggests that there are significant limitations to colonoscopy for adenoma detection due to inadequate visualization of polyps. Therefore, we recently developed ultrabright fluorescent nanoparticles (CA-dots) to highlight adenomas, and thereby, facilitate their detection. In our preliminary study, we showed that these nanoparticles preferentially bind to mouse colon adenomas and human adenoma organoids (i.e., mini-guts grown in three- dimensional environment). In this proposal, we hypothesize that CA-dots conjugated to folate groups will discriminate between adenoma and normal colon derived from colonoscopy subjects with high sensitivity and specificity. In Specific Aim 1, we will synthesize CA-dots for targeting of human adenomas. The goal of this aim is to prepare ultrabright fluorescent nanoparticles composed of cellulose acetate that demonstrate the highest accuracy in identification of colorectal adenomas. In Specific Aim 2, we will determine the efficacy of targeting fluorescent nanoparticles (CA-dots) to visually distinguish adenoma of various types from normal colon tissue. Here, we will study the efficacy of our CA-dot functionalized with folic acid to distinguish adenoma tissue from normal colon tissue biopsy specimens derived from a cohort of subjects who are referred to Duke University Hospital for removal of large (> 2 cm) adenomas. The goal of this proposal is to demonstrate efficacy of our novel fluorescent nanoparticles, CA-dots, to discriminate colon adenoma from normal colon ex vivo. Results from this study will provide preliminary data for R01-level applications to examine the application of this technology for the detection of precancerous adenomas during screening colonoscopy, which is our overarching goal.