摘要
Fluorescence imaging in the second infrared window(1000-1700 nm)has emerged as a promising approach to tumor diagnosis.However,the currently available second near-infrared(NIR-II)imaging agents are based on the“always on”modality or single biomarker activation,which are subject to limited imaging contrast,nonspecific response,and even false-positive diagnosis.Here,we developed a H2S/H+dual-stimuli responsive NIR-II fluorescent probe,WH-N3,for precise tumor delimitation and intraoperative fluorescence-guided surgical resection.WH-N3 itself is nonfluorescent,and it can only light up through synergistic activation by H2S and in the tumor acidic environment(TEM).Such a“duallock-dual-key”strategy-based activatable probe exhibited significantly higher tumor-to-normal tissue(T/N)ratios than the“always on”agent(ICG)and single parameter responsive counterpart probes in the imaging of colon tumors,which overexpresses H2S.WH-N3 was also able to visualize the tumor-derived endogenous H2S fluctuation and accurately differentiate tumor types based on H2S content discrepancy.More excitingly,under the guidance of the probe’s highly specific NIR-II fluorescence,a tiny orthotopic colon tumor with diameter down to 0.8 mm was facilely resected.We expect our dual-stimuli responsive strategy will contribute more reliable tools for specific discrimination and imaging-guided excision of tumor.
基金
This work was financially supported by the National Natural Science Foundation of China(grant no.21625503).The numerical calculations in this paper have been done on the supercomputing system in the Supercomputing Center of Wuhan University.