Oral Administration of Trifluoroacetyl Chitosan–Encapsulated Redshifted Immunofluorophore for NIR‐II Bioimaging of Colorectal Metastases

Abstract The oral administration of immunofluorophores has been limited by gastrointestinal degradation. To address this, a novel immunofluorophore (ICGM‐B9‐FCS), based on a single‐domain antibody‐dye targeting the CEACAM5 antigen, is coated with trifluoromethyl chitosan (5 mg kg −1 ) for NIR‐II bioimaging of colorectal cancer and its distant metastases. ICGM‐B9‐FCS demonstrates unique advantages over existing intraoperative tumor‐guidance bioagents, including resistance to liver metabolism, well‐retained bioaffinity (EC 50 = 58.09 nmol L −1 ), enhanced relative quantum yield (up to 12 equivalents), significant redshifts in absorption (from 783 to 957 nm), effective oral delivery to colonic metastases, and in situ exploration of the capillary‐lymphatic network transportation. These findings establish a regulatory pathway for modifying immunofluorophores as orally administered bioagents, offering innovative methods for preoperative diagnosis and intraoperative guidance in colorectal cancer.