Oral renal-clearable gold supraclusters for near-infrared II urinary diagnosis of ulcerative colitis.

Fluorescence biosensing offers a promising transformative strategy for non-invasively diagnosing diseases, but its deployment for clinical urinalysis is largely hindered by the lack of fluorescent endogenous biomarkers, insufficient detection sensitivity and specificity, and intrinsic urinary fluorescence interference. Here, we report an oral renal-clearable near-infrared II (NIR-II) fluorescent biosensor (termed supraNC@PPADT) as a synthetic exogenous biomarker for early diagnosis and therapeutic efficacy monitoring of ulcerative colitis via in vitro fluorometric urinalysis. The supraNC@PPADT biosensor comprises an Au supra-nanocluster (supraNC) core encapsulated within an acid-resistant but reactive oxygen species (ROS)-responsive poly-(1,4-phenyleneacetone dimethylene thioketal) (PPADT) protective shell. Following oral administration, this biosensor maintains high structural integrity in the healthy gastrointestinal tract and releases renal-clearable ultrasmall Au nanoclusters (Au NCs) via ROS-triggered thioketal cleavage at inflamed intestinal sites. Due to minimized background fluorescence interference, oral gavage of the supraNC@PPADT biosensor enables real-time tracking of inflamed lesions via NIR-II fluorescence imaging in an inflammatory bowel disease (IBD) murine model. We successfully validate this biosensor for early diagnosis and therapeutic efficacy monitoring of IBD in mice via NIR-II fluorometric urinalysis, achieving significantly earlier detection time and higher sensitivity than the clinical fecal calprotectin ELISA assay.