Laboratoire Physico Chimie Curie, PCC, CNRS UMR168, Institut Curie, Sorbonne University, PSL University, 75005, Paris, France.
Université Sorbonne Paris Nord, Université Paris Cité, Laboratory for Vascular Translational Science, LVTS, INSERM, UMR 1148, F‑ 93017, Bobigny, France.
Nat Commun. 2023 Aug 2;14(1):4637. doi: 10.1038/s41467-023-40258-1.
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 Fe 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.
Fe(II)诱导的铁死亡细胞死亡途径是癌症治疗的一个优势，但这引起了人们对磁性纳米粒子生物相容性的质疑。在后者中，Fe(II)被隔离在晶体结构中，只有在纳米粒子降解时才会释放出来，而这种转变还没有得到很好的理解。在这里，我们剖析了纳米粒子降解和随后 Fe(II)释放所需的化学环境。重要的是，温度是该过程的加速剂，可以通过激光介导的光热转换远程触发，这可以从纳米粒子的磁性指纹的丧失中得到证明。值得注意的是，通过比较光热诱导的纳米粒子降解模式与整体加热的模式，可以在操作过程中测量纳米尺度上产生的局部热点温度，并且可以在每个纳米粒子的附近进行测量。此外，远程光热辐照可以在肿瘤球体模型中的癌细胞内加速降解，其效率与纳米粒子的内吞进展状态相关。在球体水平上对 Fe 释放、ROS 生成、脂质过氧化和细胞死亡进行高通量成像定量，证实了由于纳米粒子水平的光热降解而产生的协同热铁死亡治疗。
