Collagen‐Anchoring Polymer Dots Enable Rapid and Precise Detection of Microlesions in Inflammatory Bowel Disease through Perivascular Matrix Accumulation

Abstract Inflammatory bowel disease (IBD) poses substantial challenges in early diagnosis and the detection of small lesions due to clinical heterogeneity and limitations of existing imaging techniques. In this study, functional polymer dots (Pdots) are developed to rapidly and precisely image microlesions by extravasating from IBD‐associated vasculature and anchoring within the perivascular matrix mediated by collagen. These Pdots are engineered with dual‐channel fluorescence (visible/NIR windows) and photoacoustic (PA) imaging capabilities, making them suitable for non‐invasive IBD diagnosis. Diagnosis using these functional Pdots can be completed within 3 h, which is significantly faster than current nanoprobes. Furthermore, the Pdots allow for continuous visualization of the IBD‐affected areas for up to 24 h. They are capable of detecting microlesions smaller than 200 µm, surpassing the resolution achieved in previous studies. Additionally, even when utilizing wide‐field stereoscopic fluorescence microscopy, the signal‐to‐background ratio (SBR) in IBD‐affected areas reaches up to 4.75. High‐resolution microvascular imaging reveals IBD‐associated intestinal vascular remodeling, including mucosal vascular dilation and submucosal pathological angiogenesis at a resolution of 2–3 µm. Notably, IBD induces a marked increase in the proportion of microvessels with diameters less than 20 µm in the cecum, Peyer's patches (PP), and mesenteric lymph nodes (MLN) of mice. This work establishes functional Pdots as promising nanoplatforms for rapid and precise IBD diagnosis by leveraging the pathological features of IBD‐affected areas. Moreover, they facilitate real‐time and high‐resolution visualization of microvasculature, offering significant potential for guiding therapeutic interventions.