School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, China.
Center for Nano Energy Materials, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi'an, 710072, China.
Biomaterials. 2021 Apr;271:120739. doi: 10.1016/j.biomaterials.2021.120739. Epub 2021 Mar 3.
Site-specific Fe generation is promising for tumor therapy. Up to now, reported materials or systems for Fe delivery do not naturally exist in the body, and their biological safety and toxicity are concerned. Herein, inspired by the natural biomineral ferrihydrite in ferritin, we synthesized monodispersed ferrihydrite nanoparticles and demonstrated a light triggered Fe generation on tumor sites. Ferrihydrite nanoparticles of 20-30 nm in diameter possessed high cellular uptake efficiency and good biocompatibility. Under common blue light illumination, a large amount of Fe could be released from ferrihydrite and promote the iron/reactive oxygen species (ROS)-related irreversible DNA fragmentation and glutathione peroxidase 4 (GPX4) inhibition, which led to the apoptosis- and ferroptosis-depended cancer cell proliferation inhibition. On mice, this method induced tumor associated macrophage (TAM) polarization from the tumor-promoting M2 type to the tumor-killing M1 type. With the intravenous pre-injection of ferrihydrite, the combinational effects of the light/Fe-approach attenuated pulmonary metastasis on mice. These results demonstrated a novel external light controlled Fe-generation approach based on biomineral, which will fully tap the anti-cancer potential of Fe in chemo-dynamic, photo-dynamic and immune-activating therapies.
基于生物矿化的肿瘤部位特异性铁生成用于癌症治疗。目前，用于铁传递的报道材料或系统在体内并不天然存在，其生物安全性和毒性令人担忧。受转铁蛋白中天然生物矿化的水铁矿的启发，我们合成了单分散的水铁矿纳米颗粒，并在肿瘤部位证明了光触发的铁生成。直径为 20-30nm 的水铁矿纳米颗粒具有较高的细胞摄取效率和良好的生物相容性。在普通的蓝光照射下，大量的铁可以从水铁矿中释放出来，并促进铁/活性氧（ROS）相关的不可逆 DNA 片段化和谷胱甘肽过氧化物酶 4（GPX4）抑制，从而导致细胞凋亡和铁死亡依赖的癌细胞增殖抑制。在小鼠中，这种方法诱导肿瘤相关巨噬细胞（TAM）从促肿瘤的 M2 型向杀伤肿瘤的 M1 型极化。通过静脉预先注射水铁矿，光/铁方法联合减轻了小鼠的肺转移。这些结果证明了一种基于生物矿化的新型外部光控铁生成方法，它将充分挖掘铁在化学动力学、光动力学和免疫激活治疗中的抗癌潜力。
