Radioisotope-mimetic molecular afterglow probe for downregulated cancer biomarker imaging

Nature Materials (2026)Cite this article Molecular afterglow imaging is a biomedical modality with high sensitivity and specificity. However, due to the short half-lives of existing afterglow agents, longitudinal imaging often requires multiple on-site reinductions. Here we report a probe with month-long afterglow luminescence and the ability to target a downregulated liver tumour biomarker. This downregulated-biomarker-activatable afterglow probe (DROP) operates through a self-sustainable photoenergy cycling reaction, during which afterglow resonance energy transfer re-excites the afterglow initiator to regenerate singlet oxygen. This process initiates new afterglow resonance energy transfer cycles, extending the afterglow duration to over 40 days. The long afterglow of DROP enables in vivo imaging over 8 h with a single light preinduction, mimicking the imaging process of radioisotopes. Moreover, DROP quickly becomes inactive in healthy liver tissues due to cytochrome P450 enzyme activity, detecting and delineating tumours as small as 1 mm in diameter for complete surgical resection in both murine and rabbit models. Overall, we provide fundamental guidelines to develop radioisotope-mimetic afterglow luminescence probes and highlight the targeting of downregulated biomarkers as a promising approach in cancer theranostics.This is a preview of subscription content, access via your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription $32.99 / 30 days cancel any timeSubscribe to this journal Receive 12 print issues and online access $259.00 per yearonly $21.58 per issueBuy this articleUSD 39.95Prices may be subject to local taxes which are calculated during checkoutData generated or analysed during this study are provided as source data or are included in the Supplementary Information. 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Development and application of a near-infrared fluorescence probe for oxidative stress based on differential reactivity of linked cyanine dyes. J. Am. Chem. Soc. 132, 2795–2801 (2010).Article CAS PubMed Google Scholar Download referencesD.D. thanks the National Natural Science Foundation of China (NSFC, 52225310) and the Fundamental Research Funds for the Central Universities, Nankai University (2122021405) for financial support. Y.Z. thanks the NSFC (22322406) for financial support. K.P. thanks the Singapore National Research Foundation (NRF) (NRF-NRFI07-20210005) and the Singapore Ministry of Education Academic Research Fund Tier 2 (MOE-T2EP30220-0010, MOE-T2EP30221-0004) for financial support. G.F. thanks the NSFC (22595402, 52473300) and Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates (2023B1212060003) for financial support. G.-Q.Z thanks the NSFC (52203171) and the Scientific Research Foundation of Hebei Educational Committee (BJK2024192) for financial support. We thank Z. Liang for providing the PDX tissues.These authors contributed equally: Guo-Qiang Zhang, Guangxue Feng.Frontiers Science Center for New Organic Matter, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences and Academy for Advanced Interdisciplinary Studies, Nankai University, Tianjin, People’s Republic of ChinaGuo-Qiang Zhang, Zhiyuan Gao, Jingtian Zhang & Dan DingState Key Laboratory of New Pharmaceutical Preparations and Excipients, MOE Key Laboratory of Medicinal Chemistry and Molecular Diagnosis, College of Pharmaceutical Sciences, Hebei University, Baoding, People’s Republic of ChinaGuo-Qiang Zhang & Longfei LiState Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, AIE Institute, School of Materials Science and Engineering, South China University of Technology, Guangzhou, People’s Republic of ChinaGuangxue FengSchool of Chemistry, Chemical Engineering and Biotechnology, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, SingaporeCheng Xu & Kanyi PuSchool of Chemistry and Chemical Engineering, Institute for Advanced Study of Life and Health, Southeast University, Nanjing, People’s Republic of ChinaYan ZhangSearch author on:PubMed Google ScholarSearch author on:PubMed Google ScholarSearch author on:PubMed Google ScholarSearch author on:PubMed Google ScholarSearch author on:PubMed Google ScholarSearch author on:PubMed Google ScholarSearch author on:PubMed Google ScholarSearch author on:PubMed Google ScholarSearch author on:PubMed Google ScholarG.-Q.Z. and G.F. contributed equally to this paper. D.D., Y.Z. and K.P. conceived the study. D.D., Y.Z., K.P., G.-Q.Z. and G.F. designed the experiments. G.-Q.Z. and Z.G. performed the chemical synthesis. G.-Q.Z. performed nanoprobe construction. G.-Q.Z., Z.G. and G.F. performed in vitro characterization. G.F. performed database analysis. L.L. performed molecular dynamics simulation. G.-Q.Z., J.Z. and Z.G. performed in vivo experiments. G.F. and C.X. drew the schematic illustration. K.P., Y.Z., D.D., G.F., C.X. and G.-Q.Z. analysed the data and drafted the manuscript.Correspondence to Yan Zhang, Kanyi Pu or Dan Ding.The authors declare no competing interests.Nature Materials thanks Hak Soo Choi, Guosheng Song and Fan Zhang for their contribution to the peer review of this work.Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary Schemes 1 and 2, Figs. 1–44 and Tables 1 and 2.Statistical source data.Statistical source data.Statistical source data.Statistical source data.Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.Reprints and permissionsZhang, GQ., Feng, G., Xu, C. et al. Radioisotope-mimetic molecular afterglow probe for downregulated cancer biomarker imaging. Nat. Mater. (2026). https://doi.org/10.1038/s41563-026-02507-8Download citationReceived: 01 May 2025Accepted: 20 January 2026Published: 19 February 2026Version of record: 19 February 2026DOI: https://doi.org/10.1038/s41563-026-02507-8Anyone you share the following link with will be able to read this content:Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative