Synergistic therapy combines multiple therapeutic approaches in one shot, thus could significantly amplify the therapeutic effects. However, how to design the desirable combination to maximize the synergistic effect is still a big challenge in cancer management. Herein, a nano-agent composed of glucose oxidase (GOx) and upconversion nanoparticles (UCNPs) were constructed for programmable starving-photodynamic synergistic cancer therapy through cascade glucose oxidation and hydrogen peroxide photolysis. In this nanoagent, GOx modulated the tumor glucose metabolism and consumed the β-D-glucose to produce H₂O₂. The glucose depletion induced “starvation” in cancer cells and caused cell death. Afterwards, the generated H₂O₂ was photolyzed by the invisible ultraviolet emission of UCNPs under near-infrared light excitation at 980 nm. The toxic hydroxyl radicals produced by photolysis further induced cancer cell death. Both in vitro and in vivo experiments confirmed that this starving-photodynamic synergistic therapy significantly outran any single therapy. This study paves an avenue to design programmable starving-photodynamic synergistic therapy for cancer management.

协同治疗一次就结合了多种治疗方法，因此可以显着增强治疗效果。然而，如何设计理想的组合以最大程度地发挥协同作用仍然是癌症治疗中的一大挑战。本文中，构建了一种由葡萄糖氧化酶（GOx）和上转换纳米颗粒（UCNPs）组成的纳米剂，用于通过级联葡萄糖氧化和过氧化氢光解来进行可编程饥饿-光动力协同癌症治疗。在这种纳米剂中，GOx调节肿瘤的葡萄糖代谢并消耗β- D-葡萄糖以产生H ₂ O ₂。葡萄糖耗竭导致癌细胞“饥饿”并导致细胞死亡。之后，生成的H ₂ O ₂在980 nm的近红外光激发下，UCNPs的不可见紫外线发射将其光解。光解产生的有毒羟基自由基进一步诱导癌细胞死亡。二者在体外和体内实验确认这饥饿光动力疗法协同显著outran任何单一疗法。这项研究为设计可饿死的光动力协同治疗癌症的方法铺平了道路。