索拉非尼 (SRF) 被认为是肝细胞癌 (HCC) 的主要治疗方法，但许多 HCC 患者中出现的 SRF 耐药性导致了不利的结果。提高 SRF 在 HCC 中的疗效仍然是一个重大挑战。 SRF 通过抑制谷胱甘肽过氧化物酶 4 (GPX4) 来诱导癌细胞中的铁死亡（一种细胞死亡形式）。该过程的有效性受到细胞铁和活性氧 (ROS) 水平低的限制。规避这一限制的一种有前途的方法是使用由磁性氧化铁纳米材料（MION）介导的细胞内磁热疗（MH）。当 MION 受到交变磁场 (AMF) 作用时，它们会升温，增强芬顿反应，从而显着增加细胞内 ROS 的产生。在这项研究中，我们探索了高性能亚铁磁涡旋域氧化铁纳米环（FVIO）促进的 MH 的能力，以增强 SRF 治疗 HCC 的有效性。 FVIO 促进的铁吸收增加显着增强了 HCC 细胞对 SRF 诱导的铁死亡的敏感性。此外，FVIO 响应 AMF 产生的纳米热进一步提高 ROS 水平，刺激脂质过氧化氢 (LPO) 产生和 GPX4 失活，从而加剧铁死亡。体外和体内动物研究均表明，将 FVIO 介导的 MH 与 SRF 相结合，主要通过增强铁死亡来显着降低细胞活力并抑制肿瘤生长，且副作用极小。这种联合疗法的有效性受到铁死亡抑制剂 Ferrostatin-1 (Fer-1) 和铁螯合剂去铁胺 (DFO) 的影响。 FVIO介导的MH和SRF的联合治疗通过促进加速铁死亡为HCC治疗提供了策略，为基于铁死亡的抗癌疗法的发展提供了不同的视角。

Sorafenib (SRF) is recognized as the primary treatment for hepatocellular carcinoma (HCC), yet the emergence of SRF resistance in many HCC patients results in unfavorable outcomes. Enhancing the efficacy of SRF in HCC remains a significant challenge. SRF works in inducing ferroptosis, a form of cell death, in cancer cells through the inhibition of glutathione peroxidase 4 (GPX4). The effectiveness of this process is limited by the low levels of cellular iron and reactive oxygen species (ROS). A promising approach to circumvent this limitation is the use of intracellular magnetic hyperthermia (MH) mediated by magnetic iron oxide nanomaterials (MIONs). When MIONs are subjected to an alternating magnetic field (AMF), they heat up, enhancing the Fenton reaction, which in turn significantly increases the production of ROS within cells. In this study, we explore the capability of MH facilitated by high-performance ferrimagnetic vortex-domain iron oxide nanoring (FVIO) to enhance the effectiveness of SRF treatment in HCC. The increased iron uptake facilitated by FVIO significantly enhances the sensitivity of HCC cells to SRF-induced ferroptosis. Moreover, the nanoheat generated by FVIO in response to an AMF further elevates ROS levels and stimulates lipid hydroperoxide (LPO) production and GPX4 inactivation, thereby intensifying ferroptosis. Both in vitro and in vivo animal studies demonstrate that combining FVIO-mediated MH with SRF significantly reduces cell viability and inhibits tumor growth, primarily through enhanced ferroptosis, with minimal side effects. The effectiveness of this combination therapy is affected by the ferroptosis inhibitor ferrostatin-1 (Fer-1) and the iron chelator deferoxamine (DFO). The combination treatment of FVIO-mediated MH and SRF offers a strategy for HCC treatment by promoting accelerated ferroptosis, presenting a different perspective for the development of ferroptosis-based anticancer therapies.