Abstract: | There is a great challenge to overcome the limitation of tissue penetration depth, while maximizing the benefit of light‐triggered biochemical cascades in a well‐defined mode simultaneously. Here, a new method of near‐infrared (NIR) light‐triggered release of nitric oxide (NO) by developing upconversion nanoparticles (UCNPs)‐based conjugate chemistry is reported. As the key nanotransducer in the design, core–shell‐structured UCNPs are encapsulated with a layer of SiO2 and then covalently linked with a potent NO‐releasing donor (S‐nitroso‐N‐acetyl‐dl ‐penicillamine, SNAP). It is featured with highly localized breakage of chemical bonds of SNAP molecules by NIR–UV upconversion, enabling simultaneous NO release in a light dosage‐dependent manner. The biological effects of NO releasing are demonstrated by cellular imaging and inhibition of platelet aggregation from blood samples. This work provides a flexible and robust platform to generate cell‐signaling gas molecules trigged by NIR laser with deep tissue penetration. |