Development of Pluoronic nanoparticles of fluorocoxib A for endoscopic fluorescence imaging of colonic adenomas

SIGNIFICANCE: Current white light colonoscopy suffers from many limitations that allow 22% to 32% of preneoplastic lesions to remain undetected. This high number of false negatives contributes to the appearance of interval malignancies, defined as neoplasms diagnosed between screening colonoscopies at a rate of 2% to 6%. AIM: The shortcomings of today’s white light-based colorectal cancer screening are addressed by colonoscopic fluorescence imaging of preneoplastic lesions using targeted fluorescent agents to enhance contrast between the lesion and the surrounding normal colonic epithelium. APPROACH: We describe the development of Pluronic(®) nanoparticles of fluorocoxib A (FA), a fluorescent cyclooxygenase-2 (COX-2) inhibitor that enables targeted imaging of inflammation and cancer in numerous animal models, for endoscopic florescence imaging of colonic adenomas. RESULTS: We formulated FA, a fluorescent COX-2 inhibitor, or fluorocoxib negative control (FNC), a nontargeted fluorophore and a negative control for FA, in micellar nanoparticles of FDA approved Pluronic tri-block co-polymer using a bulk solvent evaporation method. This afforded FA-loaded micellar nanoparticles (FA-NPs) or FNC-loaded micellar nanoparticles (FNC-NPs) with the hydrodynamic diameters ([Formula: see text]) of [Formula: see text] and [Formula: see text] and the zeta potentials ([Formula: see text]) of [Formula: see text] and [Formula: see text] , respectively. We intravenously injected B6;129 mice bearing colonic adenomas induced by azoxymethane and dextran-sodium sulfate with FA-loaded Pluronic nanoparticles (FA-NPs). The diffusion-mediated local FA release and its binding to COX-2 enzyme allowed for clear detection of adenomas with high signal-to-noise ratios. The COX-2 targeted delivery and tumor retention were validated by negligible tumor fluorescence detected upon colonoscopic imaging of adenoma-bearing mice injected with Pluronic nanoparticles of FNC or of animals predosed with the COX-2 inhibitor, celecoxib, followed by intravenous dosing of FA-NPs. CONCLUSIONS: These results demonstrate that the formulation of FA in Pluronic nanoparticles overcomes a significant hurdle to its clinical development for early detection of colorectal neoplasms by fluorescence endoscopy.