Activatable biomimetic probe with aggregation-induced emission characteristics for non-invasive monitoring of allograft rejection.

: Background: Allograft rejection remains a major barrier to the long-term success of organ transplantation. The current gold standard for diagnosis-tissue biopsy is invasive and carries inherent risks, including sampling errors, procedural complications, and high costs. There is a pressing need for an efficient, non-invasive strategy for the early detection and monitoring of transplant rejection. Methods: We developed a macrophage-targeted, activatable imaging probe () by encapsulating the H₂O₂-responsive aggregation-induced emission (AIE) molecule into glucan particles (GPs) via electrostatic and hydrophobic interactions. The probe's responsiveness to H₂O₂ was characterized using UV-vis and fluorescence spectroscopy. Biocompatibility was evaluated through hemolysis assays, immunogenicity testing, biochemical analysis, and histopathology. Macrophage polarization and probe specificity were assessed using confocal laser scanning microscopy (CLSM), flow cytometry (FCM), and ELISA. A murine dorsal skin transplantation model was established to dynamically monitor graft rejection and the therapeutic efficacy of FK506, using fluorescence imaging at postoperative days (POD) 1, 3, 5, and 7. Pathological validation was performed via H&E staining and immunofluorescence. Results: exhibited excellent biosafety, with low cytotoxicity, minimal hemolytic activity, low immunogenicity, and negligible organ toxicity. Upon oral administration, the fluorescence signal of was selectively activated by M1 macrophages, enabling early and sensitive detection of transplant rejection. Moreover, a single oral dose allowed real-time tracking of immunosuppressive therapy with FK506 Conclusion: represent a promising non-invasive platform for early diagnosis and longitudinal monitoring of transplant rejection and therapeutic response, with strong translational potential in solid organ transplantation.