Oral Butyrate‐Functionalized Magnetic Nanorobots for Targeted Exosome Transport in the Theranostics of Early‐Stage Colorectal Cancer

ABSTRACT Early detection and intervention are critical to reducing colorectal cancer (CRC) mortality. Although tumor‐derived exosomes (TDEs) are promising liquid biopsy biomarkers, their extremely low abundance in peripheral blood during early carcinogenesis severely limits clinical utility for early diagnosis. Here, we report a theranostic magnetic nanorobot (MNP‐BC), comprising Fe 3 O 4 @SiO 2 nanoparticles co‐functionalized with butyrate and anti‐CD147 antibody. Oral administration followed by magnetic guidance, MNP‐BC accumulates at colonic tumor sites, where butyrate selectively induces cancer cell apoptosis, boosts CD8 + T‐cell cytotoxicity, and preserves intestinal barrier integrity. Concurrently, the anti‐CD147 antibody moiety captures TDEs in situ. Following monocarboxylate transporter–mediated uptake, intracellular butyrate metabolism releases the MNP–TDEs complex into circulation, thereby enriching plasma TDEs for magnetic isolation and noninvasive detection. In early‐stage CRC mice, MNP‐BC markedly suppressed tumor progression and facilitated sensitive diagnosis via TDEs signal amplification. This work introduces an integrated “TDEs signal amplification–sensitive diagnosis–in situ therapy” platform, offering a rationally engineered strategy to address key translational barriers in early CRC detection and intervention.