Activatable Nanoprobes for Dual‐Modal NIR‐II Photoacoustic and Fluorescence Imaging of Hydrogen Sulfide in Colon Cancer

High hydrogen sulfide (H2S) expression has been shown to play a crucial role in tumor growth and proliferation in colon cancer. So far, most probes used for monitoring H2S offer single‐modal imaging, which makes the collection of accurate information for tumor diagnosis difficult. In the present study, a novel dual‐modal imaging probe in the second near‐infrared (NIR‐II, 950‐1700) window is proposed and constructed by coating a uniform shell of polydopamine (PDA) on the surface of cuprous oxide (Cu2O)‐conjugated downconversion nanoparticles (DCNPs). Of note, DCNP‐Cu2O@PDA is in the “on” state, with emission centered at 1550 nm (irradiation using a 980nm laser) in non‐neoplastic tissues. Colon tumors with endogenous H2S overexpression can induce the in situ transformation of Cu2O to copper sulfide (Cu2‐XS）. Owing to the competitive absorption between Cu2‐XS and DCNPs at a wavelength of 980 nm, the generated DCNP‐Cu2‐XS@PDA exhibits a quenched NIR‐II fluorescence (FL) signal. Meanwhile, Cu2‐XS exhibits a strong absorbance at 1250 nm, enhancing the NIR‐II photoacoustic (PA) signal accompanied by NIR‐II FL attenuation. The switching in PA and FL signals at the tumor site offered “double assurances” for the accurate monitoring of H2S. A novel dual‐modal imagingprobe in the second near‐infrared (NIR‐II) window is developed with “double assurances” for the accurate imaging and monitoring of H2S in vivo.