Citation: Qian Jia, Haohao Yan, Yuanyuan Jia, Shuying Liu, Yanbin Feng, Bingqian Chen, Changhong Shi, Xiaojie Xu, Ruili Zhang, Zhongliang Wang. Rapid and precise intraoperative identification of metastatic lymph nodes using a pH‑activated nanoprobe[J]. Chinese Chemical Letters, ;2026, 37(12): 112359. doi: 10.1016/j.cclet.2026.112359 shu

Rapid and precise intraoperative identification of metastatic lymph nodes using a pH‑activated nanoprobe

Qian Jia ^{a, b, 1} ,
Haohao Yan ^{a, 1} ,
Yuanyuan Jia ^{a, 1} ,
Shuying Liu ^c ,
Yanbin Feng ^a ,
Bingqian Chen ^a ,
Changhong Shi ^{d, *,} ,
Xiaojie Xu ^{a, *,} ,
Ruili Zhang ^{a, *,} ,
Zhongliang Wang ^{a, *,}

a.
Lab of Molecular Imaging and Translational Medicine (MITM), Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi’an 710126, China
b.
Guangzhou Institute of Technology, Xidian University, Guangzhou 510000, China
c.
Department of Pathology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, China
d.
Laboratory Animal Center, Air Force Medical University, Xi’an 710032, China

changhong@fmmu.edu.cn

xuxiaojie@xidian.edu.cn

rlzhang@xidian.edu.cn

wangzl@xidian.edu.cn

Received Date: 22 September 2025
Revised Date: 26 December 2025
Accepted Date: 3 January 2026
Available Online: 5 January 2026

Figures(6)

The sensitive and specific identification of lymph node (LN) metastasis is critical for cancer staging and guiding intraoperative decisions. However, the inability to accurately distinguish metastatic from healthy LNs represents a critical gap in oncologic imaging. Here, we transform the conventional near-infrared (NIR) dye indocyanine green (ICG) into a pH-activatable probe (denoted as ICCPs) for the precise detection of lymphatic metastasis. The probe design utilizes a pH-sensitive calcium phosphate nanocarrier to induce a fluorescent “OFF” state via aggregation-caused quenching (ACQ). Upon exposure to the acidic microenvironment characteristic of metastatic lesions, the nanocarrier rapidly disassembles, triggering a robust fluorescent “ON” signal. Through comprehensive in vitro and in vivo validation in a metastatic LNs model, we demonstrate that ICCPs achieve superior specificity compared to free ICG and Evans blue. The probe accurately identified primary tumors and, crucially, allowed for the precise differentiation between metastatic and normal LNs. This work establishes ICCPs as a highly promising tool for clinical translation, offering a solution for high-precision, real-time intraoperative guidance in cancer surgery.
- Molecular imaging,
- Activated probes,
- Intraoperative imaging,
- Lymph nodes identification
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