Ferroptosis-based nanomedicine has drawn increasing attention in antitumor therapy because of the advantages of this unconventional mode of apoptosis, but the difficulties of delivery to the tumor site and surface-to-core penetration after arrival seriously hinder further clinical transformation and application. Herein, we propose an unprecedented strategy of injecting magnetic nanodroplets (MNDs) to solve these two longstanding problems. MNDs are nanocarriers that can carry multifunctional drugs and imaging materials. MNDs can effectively accumulate in the tumor site by active tumor targeting (multifunctional drugs) and passive tumor targeting (enhanced permeability and retention effect), allowing diffusion of the MNDs from the surface to the core through mild-temperature magnetic fluid hyperthermia (MHT) under multimodal imaging guidance. Finally, the ferroptosis pathway is activated deep within the tumor site through the drug release. This approach was inspired by the ability of mild-temperature MHT to allow MNDs to quickly pass through the blood vessel-tumor barrier and deeply penetrate the tumor tissue from the surface to the core to amplify the antitumor efficacy of ferroptosis. This strategy is termed as “thermoferroptosis sensitization”. Importantly, this behavior can be performed under the guidance of multimodal imaging, making the design of MNDs for cancer therapy safer and more reasonable.

基于铁死亡的纳米药物由于这种非常规细胞凋亡模式的优势，在抗肿瘤治疗中越来越受到关注，但递送至肿瘤部位和到达后的表面至核心渗透的困难严重阻碍了进一步的临床转化和应用。在此，我们提出了一种前所未有的注入磁性纳米液滴 (MND) 的策略来解决这两个长期存在的问题。MND 是可以携带多功能药物和成像材料的纳米载体。MNDs可以通过主动肿瘤靶向（多功能药物）和被动肿瘤靶向（增强通透性和保留作用）有效地在肿瘤部位聚集，使MNDs通过温和的温度磁流体热疗（MHT）从表面扩散到核心。多模态成像引导。最后，铁死亡途径通过药物释放在肿瘤部位深处被激活。这种方法的灵感来自于温和的 MHT 能够让 MNDs 快速穿过血管-肿瘤屏障并从表面深入穿透肿瘤组织到核心，以放大铁死亡的抗肿瘤功效。这种策略被称为“thermoferroptosis sensitization”。重要的是，这种行为可以在多模态成像的指导下进行，使得用于癌症治疗的 MND 设计更加安全合理。这种方法的灵感来自于温和的 MHT 能够让 MNDs 快速穿过血管-肿瘤屏障并从表面深入穿透肿瘤组织到核心，以放大铁死亡的抗肿瘤功效。这种策略被称为“thermoferroptosis sensitization”。重要的是，这种行为可以在多模态成像的指导下进行，使得用于癌症治疗的 MND 设计更加安全合理。这种方法的灵感来自于温和的 MHT 能够让 MNDs 快速穿过血管-肿瘤屏障并从表面深入穿透肿瘤组织到核心，以放大铁死亡的抗肿瘤功效。这种策略被称为“thermoferroptosis sensitization”。重要的是，这种行为可以在多模态成像的指导下进行，使得用于癌症治疗的 MND 设计更加安全合理。