A smart nanoplatform for synergistic starvation, hypoxia-active prodrug treatment and photothermal therapy mediated by near-infrared-II light

[Display omitted] •Combination of GOx with hypoxia-active tirapazamine prodrug enhances hypoxia and promotes the curative effect.•High photothermal conversion efficiency (44.7%) has been achieved.•NIR-II fluorescence imaging tracks the therapeutic process.•A synergistic starvation, hypoxia-active prodrug treatment and photothermal therapy is realized. Synergistic therapy with different treatment mechanisms is an emerging strategy to improve antitumor efficiency. Here, a diversified nanoplatform (Ag2S@MSN-TGF) is synthesized by coating mesoporous silica on Ag2S nanoparticles (NPs), followed by loading hypoxia-active prodrug (tirapazamine) insides the mesoporous silica and coating glucose oxidase (GOx) on the surface. Considering that the degree of hypoxia in tumors is not high enough, GOx is combined with hypoxia-active tirapazamine prodrug, and two important functions are realized. One is the consumption of oxygen to enhance the hypoxic environment and promote the curative effect of tirapazamine, and the other is the consumption of glucose to achieve starvation treatment. Additionally, we take the lead in using Ag2S NPs for second near-infrared (NIR-II, 1064 nm) excited photothermal therapy (PTT). The photothermal conversion efficiency (44.7%) of Ag2S@MSN-TGF is even better than that under 808 nm laser irradiation (38.2%). Finally, in vivo NIR-II fluorescence imaging well demonstrated that Ag2S@MSN-TGF can offer an obvious tracking effect for the therapeutic process. Therefore, superior to any single therapeutic mode, our designed Ag2S@MSN-TGF demonstrates an excellent tumor inhibition effect in vitro and in vivo due to synergistic starvation, hypoxia-active prodrug treatment and PTT effect, suggesting the significant prospect of NIR-II imaging guided antitumor therapy.