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

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 (EC₅₀ = 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.