Nitric oxide (NO) gas therapy has been regarded as a promising strategy for cancer treatment. However, its therapeutic efficiency is still unsatisfying due to the limitations of monotherapy. Previous preclinical and clinical studies have shown that combination therapy could significantly enhance therapeutic efficiency. Herein, a graphene oxide (GO)-L-arginine (L-Arg, a natural NO donor) hybrid nanogenerator is developed followed by surface functionalization of soybean lecithin (SL) for synergistic enhancement of cancer treatment through photothermal and gas therapy. The resultant GO-Arg-SL nanogenerator not only exhibited good biocompatibility and excellent endocytosis ability, but also exhibited excellent photothermal conversion capability and high sensitivity to release NO within tumor microenvironment via inducible NO synthase (iNOS) catalyzation. Moreover, the produced hyperthermia and intracellular NO could synergistically kill cancer cells both in vitro and in vivo. More importantly, this nanogenerator can efficiently eliminate tumor while inhibiting the tumor recurrence because of the immunogenic cell death (ICD) elicited by NIR laser-triggered hyperthermia and the immune response activation by massive NO generation. We envision that the GO-Arg-SL nanogenerator could provide a potential strategy for synergistic photothermal and gas therapy.

一氧化氮（NO）气体疗法被认为是一种有前途的癌症治疗策略。然而，由于单一疗法的局限性，其治疗效果仍不能令人满意。先前的临床前和临床研究表明，联合治疗可以显着提高治疗效率。在此，开发了一种氧化石墨烯（GO）-L-精氨酸（L-Arg，一种天然的NO供体）杂化纳米发电机，然后对大豆卵磷脂（SL）进行表面功能化，以通过光热和气体疗法协同增强癌症治疗。所得GO-Arg-SL纳米发电机不仅表现出良好的生物相容性和优异的内吞能力，而且表现出优异的光热转换能力和通过在肿瘤微环境中释放NO的高灵敏度。诱导型 NO 合酶 (iNOS) 催化。此外，产生的热疗和细胞内 NO 可以在体外和体内协同杀死癌细胞。更重要的是，由于近红外激光触发的热疗引起的免疫原性细胞死亡（ICD）和大量NO产生的免疫反应激活，这种纳米发电机可以有效地消除肿瘤，同时抑制肿瘤复发。我们设想 GO-Arg-SL 纳米发电机可以为协同光热和气体治疗提供潜在的策略。