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Nanoscale metal-organic frameworks (nano MOFs) have emerged as a promising biomedical nanoplatform because of their unique properties.However,the exploration ofnano MOFs in photoacoustic (PA) imaging is still limited.Here,a novel hydrogen sulfide (H2S)-activated nano copper-based MOF (Cu-MOF) was developed as a near-infrared (NIR) ratiometric PA probe for in vivo monitoring of endogenous H2S level and orthotopic colorectal cancer imaging via in situ reaction of nano Cu-MOFs with endogenous H2S that is closely associated with tumor growth and proliferation in colon cancer.The synthesized nano Cu-MOFs displayed excellent PA responsiveness towards tumor H2S level with high selectivity and rapid kinetics.The result suggests the developed probe may provide a unique opportunity to investigate the malignant behaviors of H2S-associated events in vivo.