A 1064 nm triggered photosensitizer and photothermal induce nitric oxide release for in situ peroxynitrite generation to combine tumor therapy.

Most traditional photosensitizers (PSs) are excited by visible light or the first near-infrared window (NIR-I) exhibited high tissue scattering and shallow less tissue penetration depth. Besides, single phototherapy has the disadvantage of poor treatment effect. Herein, the three PSs were designed and synthesized. Among them, the ISO-HZF molecule can be excited by near-infrared-II window laser (NIR-II, 1064 nm), resulting in efficient generation of superoxide anions (O2• -) and achieving strong photothermal conversion. To achieve controlled release of nitric oxide (NO), ISO-HZF was further co-assembled with the NO donor S-Nitroso-N-acetyl-DL-penicillamine (SNAP), forming ISO-HZF/S nanoparticle (ISO-HZF/S NPs). Under 1064 nm laser irradiation, ISO-HZF/S NPs can generate high temperature to trigger NO production, which rapidly reacts with O2• - to form highly cytotoxic peroxynitrite (ONOO-), possessing strong oxidizing and nitration capabilities. The results of both in vitro and in vivo experiments indicate that the combined phototherapy and NO gas therapy can efficiently kill tumor cells. Collectively, this work provides a useful guideline for the design and synthesis of NIR-II light-activated PSs and combined treatment with NO gas.