Red Cell Membrane-Coating Prussian Blue for Combined Photothermal with NO Gas Therapy to Nasopharyngeal Carcinoma

Nitric oxide (NO) gas molecules have demonstrated remarkable anti-tumor effects and minimal susceptibility to drug resistance, establishing as a promising modality for effective tumor treatment. However, how to realize its stable and efficient delivery in vivo is still a challenge. In this study, we have developed a heat-responsive biomimetic nano erythrocyte (M/B@R) by loading the NO donor (BNN6) onto the mesoporous Prussian blue (M-PB) and subsequently enveloping them with red blood cell membranes. The preserved integrity of the red blood cell membrane (RBCm) structure could ensure its excellent biosafety, prolong its circulation time within the bloodstream and then enhance the accumulation of BNN6 at tumor sites. When M/B@R is stimulated by near-infrared light (NIR-II, 808 nm) irradiation, the nanoparticle could generate significant heat for photothermal therapy (PTT) by the characteristic NIR absorption of M-PB and then NO also could be efficiently released. The generated NO further facilitates the formation of ONOO−, a highly toxic species to the tumor, while also alleviating tumor hypoxia. Remarkably, M/B@R, with NIR as the excitation source, induces the combined lethality through hyperthermia, DNA damage, and tumor hypoxia relief. This novel combination strategy provides a new avenue for PTT/NO-induced cancer therapy.