2. Academic Validation
  3. Granzyme B activated near-infrared-II ratiometric fluorescent nanoprobe for early detection of tumor response to immunotherapy

Granzyme B activated near-infrared-II ratiometric fluorescent nanoprobe for early detection of tumor response to immunotherapy

  • Nat Commun. 2025 Aug 28;16(1):8054. doi: 10.1038/s41467-025-63311-7.
Lei Ding # 1 2 3,  Xiaolong Zhang # 4 5,  Peiyuan Wang 3 6,  Jianmei Ke 1 2 3,  Yang Zhou 3,  Ming Wu 3,  Zuwu Wei 3,  Yanbing Cao 3,  Hongsheng Li 3,  Geng Chen 3,  Guangwei Zheng 3,  Yongyi Zeng 7 8,  Maochun Hong 9 10 11,  Xiaolong Liu 12
Affiliations

Affiliations

  • 1 School of Rare Earths, University of Science and Technology of China, Hefei, P. R. China.
  • 2 Ganjiang Innovation Academy, Chinese Academy of Sciences, Ganzhou, P. R. China.
  • 3 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P. R. China.
  • 4 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P. R. China. xiaolongdo@gmail.com.
  • 5 Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, P. R. China. xiaolongdo@gmail.com.
  • 6 State Key Laboratory of Structure Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, P. R. China.
  • 7 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P. R. China. lamp197311@126.com.
  • 8 Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, P. R. China. lamp197311@126.com.
  • 9 School of Rare Earths, University of Science and Technology of China, Hefei, P. R. China. hmc@fjirsm.ac.cn.
  • 10 Ganjiang Innovation Academy, Chinese Academy of Sciences, Ganzhou, P. R. China. hmc@fjirsm.ac.cn.
  • 11 State Key Laboratory of Structure Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, P. R. China. hmc@fjirsm.ac.cn.
  • 12 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P. R. China. xiaoloong.liu@gmail.com.
  • # Contributed equally.
PMID: 40877261 DOI: 10.1038/s41467-025-63311-7
Abstract

Non-invasive optical imaging tools for early detecting anti-tumor immune responses are crucial for precision Cancer Immunotherapy. However, current probes often suffer from low imaging depth, single imaging channel, and inadequate quantification, hindering their in vivo applications. Here we develop a rare-earth-based NIR-II fluorescence ratiometric nanoprobe (DCGA) for in vivo real-time, precise, and non-invasive visualization of granzyme B (GzmB) activity, a key effector in T cell-mediated antitumor immunity, for early prediction of immunotherapy efficacy. The Nd/Er co-doped DCGA nanoprobe features NIR-II dual-emission ratiometric detection with self-calibrated target response signals, addressing challenges like uneven probe distribution and nonspecific signal interference. In vivo NIR-II ratiometric imaging reveals that GzmB activity well correlates with cytotoxic T cell responses and tumor growth, and can effectively distinguish responders from non-responders in both Hepa 1-6 tumor xenograft models and patient-derived xenograft models. Our DCGA probe shows promise for dynamic, real-time, non-invasive molecular imaging of T cell activation in deep tissues, offering effective support for tumor immunotherapy studies, precision medicine, and personalized diagnostics.

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