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Rogalla, S.* ; Flisikowski, K.* ; Gorpas, D. ; Mayer, A.T.* ; Flisikowska, T.* ; Mandella, M.J.* ; Ma, X. ; Casey, K.M.* ; Felt, S.A.* ; Saur, D.* ; Ntziachristos, V. ; Schnieke, A.* ; Contag, C.H.* ; Gambhir, S.S.* ; Harmsen, S.*

Biodegradable fluorescent nanoparticles for endoscopic detection of colorectal carcinogenesis.

Adv. Func. Mat. 29:1904992 (2019)

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Early and comprehensive endoscopic detection of colonic dysplasia-the most clinically significant precursor lesion to colorectal adenocarcinoma-provides an opportunity for timely, minimally invasive intervention to prevent malignant transformation. Here, the development and evaluation of biodegradable near-infrared fluorescent silica nanoparticles (FSN) that have the potential to improve adenoma detection during fluorescence-assisted white-light colonoscopic surveillance in rodent and human-scale models of colorectal carcinogenesis is described. FSNs are biodegradable (t(1/2) of 2.7 weeks), well-tolerated, and enable detection and delineation of adenomas as small as 0.5 mm(2) with high tumor-to-background ratios. Furthermore, in the human scale, APC(1311/+) porcine model, the clinical feasibility and benefit of using FSN-guided detection of colorectal adenomas using video-rate fluorescence-assisted white-light endoscopy is demon-strated. Since nanoparticles of similar size (e.g., 100-150 nm) or composition (i.e., silica and silica/gold hybrid) have already been successfully translated to the clinic, and clinical fluorescent/white-light endoscopy systems are becoming more readily available, there is a viable path towards clinical translation of the proposed strategy for early colorectal cancer detection and prevention in high-risk patients.

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