由于其固有特性，二维 (2D) 铋 (bismuthene) 可作为肺癌的多模式纳米治疗剂，通过多种机制发挥作用，包括光热疗法 (PTT)、磁场诱导热疗 (MH)、免疫原性细胞死亡（ICD）和铁死亡。为了研究这种可能性，我们从 3D 层状铋的剥离中合成了铋烯，这是通过我们开发的涉及表面活性剂辅助化学还原的简便方法制备的，特别注重提高其磁性。在肺腺癌细胞中同时暴露于光和磁场后，铋烯纳米片显示出较高的体外和体内抗癌活性。只有当光和磁场一起应用时，与单一治疗组相比，我们才能实现最高的抗癌活性。我们进一步表明，这种组合治疗策略涉及 ICD 依赖性机制。除了 ICD 之外，除了细胞凋亡途径外，基于 Bismuthene 的 PTT 和 MH 还导致体外和体内铁死亡机制的增加。最后，人全血中的溶血和人外周血单核细胞中的多种测定表明，铋烯纳米片具有生物相容性，并且不会改变免疫功能。这些结果表明 Bismuthene 有潜力作为生物相容性平台，为肺癌提供多种治疗方法。© 2023 作者。

Thanks to its intrinsic properties, two-dimensional (2D) bismuth (bismuthene) can serve as a multimodal nanotherapeutic agent for lung cancer acting through multiple mechanisms, including photothermal therapy (PTT), magnetic field-induced hyperthermia (MH), immunogenic cell death (ICD), and ferroptosis. To investigate this possibility, we synthesized bismuthene from the exfoliation of 3D layered bismuth, prepared through a facile method that we developed involving surfactant-assisted chemical reduction, with a specific focus on improving its magnetic properties. The bismuthene nanosheets showed high in vitro and in vivo anti-cancer activity after simultaneous light and magnetic field exposure in lung adenocarcinoma cells. Only when light and magnetic field are applied together, we can achieve the highest anti-cancer activity compared to the single treatment groups. We have further shown that ICD-dependent mechanisms were involved during this combinatorial treatment strategy. Beyond ICD, bismuthene-based PTT and MH also resulted in an increase in ferroptosis mechanisms both in vitro and in vivo, in addition to apoptotic pathways. Finally, hemolysis in human whole blood and a wide variety of assays in human peripheral blood mononuclear cells indicated that the bismuthene nanosheets were biocompatible and did not alter immune function. These results showed that bismuthene has the potential to serve as a biocompatible platform that can arm multiple therapeutic approaches against lung cancer.© 2023 The Authors.