铁离子（Fe(II)）诱导的铁死亡途径是癌症治疗中的一个优势，然而，这也对磁性纳米颗粒的生物相容性提出了质疑。在后者中，Fe(II)被固定在晶体结构中，只有在纳米颗粒降解时才会释放，这一转变并不被很好地理解。在本文中，我们剖析了纳米颗粒降解及随后Fe(II)释放所需的化学环境。重要的是，温度作为促进过程的加速剂，并且可以通过激光介导的光热转化远程触发，这可以通过纳米颗粒磁指纹的丧失来证实。非常引人注目的是，在纳米尺度上生成的局部热点温度可以通过比较光热诱导的纳米颗粒降解模式与全局加热模式之间的差异，在每个纳米颗粒的附近进行实时测量。此外，远程光热照射加速了肿瘤球模型中癌细胞内的降解过程，其效率与纳米颗粒的内吞进展状态相关。通过高通量成像对肿瘤球水平的Fe2+释放、ROS产生、脂质过氧化和细胞死亡进行量化，确认了光热降解对纳米颗粒层面上的热-铁死亡治疗的协同作用。© 2023. 作者。

The Fe(II)-induced ferroptotic cell death pathway is an asset in cancer therapy, yet it calls into question the biocompatibility of magnetic nanoparticles. In the latter, Fe(II) is sequestered within the crystal structure and is released only upon nanoparticle degradation, a transition that is not well understood. Here, we dissect the chemical environment necessary for nanoparticle degradation and subsequent Fe(II) release. Importantly, temperature acts as an accelerator of the process and can be triggered remotely by laser-mediated photothermal conversion, as evidenced by the loss of the nanoparticles' magnetic fingerprint. Remarkably, the local hot-spot temperature generated at the nanoscale can be measured in operando, in the vicinity of each nanoparticle, by comparing the photothermal-induced nanoparticle degradation patterns with those of global heating. Further, remote photothermal irradiation accelerates degradation inside cancer cells in a tumor spheroid model, with efficiency correlating with the endocytosis progression state of the nanoparticles. High-throughput imaging quantification of Fe2+ release, ROS generation, lipid peroxidation and cell death at the spheroid level confirm the synergistic thermo-ferroptotic therapy due to the photothermal degradation at the nanoparticle level.© 2023. The Author(s).