{"title":"Activatable biomimetic probe with aggregation-induced emission characteristics for non-invasive monitoring of allograft rejection.","authors":"Mengdan Ding, Fang He, Shuangze Han, Wuqi Zhou, Tian Huang, Nan Cui, Yuanting Quan, Wenqu Li, Wenyuan Wang, Tang Gao, Mingxing Xie, Li Zhang","doi":"10.7150/thno.110866","DOIUrl":null,"url":null,"abstract":"<p><p><b>Abstract</b>: 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 (<b>MTBPB/GPs</b>) by encapsulating the H₂O₂-responsive aggregation-induced emission (AIE) molecule <b>MTBPB</b> 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 <i>in vivo</i> fluorescence imaging at postoperative days (POD) 1, 3, 5, and 7. Pathological validation was performed via H&E staining and immunofluorescence. Results: <b>MTBPB/GPs</b> exhibited excellent biosafety, with low cytotoxicity, minimal hemolytic activity, low immunogenicity, and negligible organ toxicity. Upon oral administration, the fluorescence signal of <b>MTBPB/GPs</b> 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<b>.</b> Conclusion: <b>MTBPB/GPs</b> 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.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 13","pages":"6572-6592"},"PeriodicalIF":13.3000,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160014/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Theranostics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7150/thno.110866","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract: 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 (MTBPB/GPs) by encapsulating the H₂O₂-responsive aggregation-induced emission (AIE) molecule MTBPB 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 in vivo fluorescence imaging at postoperative days (POD) 1, 3, 5, and 7. Pathological validation was performed via H&E staining and immunofluorescence. Results: MTBPB/GPs exhibited excellent biosafety, with low cytotoxicity, minimal hemolytic activity, low immunogenicity, and negligible organ toxicity. Upon oral administration, the fluorescence signal of MTBPB/GPs 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: MTBPB/GPs 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.
期刊介绍：
Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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