目前的白光结肠镜检查存在许多限制，导致22%至32%的潜在恶变病变无法被检测出来。这种高错误阴性率导致间隔性恶性肿瘤的出现，其定义为在筛查结肠镜检查之间诊断的肿瘤发生率为2%至6%。通过使用有针对性的荧光探针增强病变和周围正常结肠上皮之间对比度的结肠荧光成像技术，可以解决目前基于白光的结直肠癌筛查的缺点。我们描述了使用靶向荧光偶联剂进行直肠腺瘤的内窥镜荧光成像的荧光环氧合酶-2（COX-2）荧光成像剂，即Fluorocoxib A（FA）的Pluronic®纳米粒子的制备过程。我们使用FDA批准的Pluronic三嵌段共聚物，采用体积溶剂蒸发法制备FA荧光分子或Fluorocoxib阴性对照（FNC）的胶束型纳米粒子，FNC为一种非靶向性荧光物质，是FA的对照，制备了带有FA或FNC的胶束型纳米粒子（FA-NPs或FNC-NPs），其流体力学直径（Dh）分别为45.7±2.5nm和44.9±3.8nm，噻二唑甲烷和右旋糖醚诱导的结肠腺瘤的小鼠B6;129注射了带有FA的Pluronic纳米粒子（FA-NPs）。扩散介导的局部FA释放及其与COX-2酶的结合使腺瘤的高信噪比成像得以清晰检测。通过内窥镜成像检测注射FNC的腺瘤小鼠或先用COX-2抑制剂Celecoxib给小鼠注射FA-NPs后检测，证实了COX-2的靶向传递和肿瘤保留。这些结果表明，在Pluronic纳米粒子中配制FA克服了其用于荧光内窥镜早期检测结直肠肿瘤的临床开发的重大障碍。© 2023 The Authors.

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%.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.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.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 ( D h ) of 45.7 ± 2.5    nm and 44.9 ± 3.8    nm and the zeta potentials ( ζ ) of - 1.47 ± 0.3    mV and - 1.64 ± 0.5    mV , 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.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.© 2023 The Authors.