Low dose soft X-ray-controlled deep-tissue long-lasting NO release of persistent luminescence nanoplatform for gas-sensitized anticancer therapy

Nitric oxide (NO)-based gas therapy is emerged as a new adjunct anti-tumor treatment method, which has triggered a great research interest. Nevertheless, due to the short half-life of NO gas in vivo, it is of significance to develop NO-gas based gasotransmitter with controllable NO release for deep-tissue anti-tumor therapy. Herein, a novel soft X-ray activated persistent luminescence nanotransducer is designed for controllable and long-lasting NO release and deep-tissue anti-cancer therapy by integrating ZnGa2O4:Mn (ZGO:Mn) nanoparticles with light-responsive NO donor (RBS). With the merits of the ultra-low dosage (down to 0.9 mGy) soft X-ray activated persistent luminescence from small sized ZGO:Mn, continuous NO release is achieved for about 40 min after stopping the irradiation of X-ray. Moreover, the green persistent luminescence can be renewably activated by in-situ soft X-ray irradiation, leading to the repeatable long-lasting NO release in deep tissue (up to 24 mm). And the designed NO-releasing platform presents efficient in vitro and in vivo anti-cancer therapy. Therefore, the designed persistent luminescence-based NO gasotransmitter provides a new NO-releasing strategy for depth-independent gas-sensitized therapeutic applications.