College of Materials Science and Engineering, Research Center of Magnetic and Electronic Materials, Zhejiang University of Technology, Hangzhou, 310014, China.
Department of Radiation Oncology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.
Adv Sci (Weinh). 2024 Sep;11(36):e2403935. doi: 10.1002/advs.202403935. Epub 2024 Jul 30.
Chemodynamic therapy (CDT) is a novel tumor treatment method by using hydroxyl radicals (OH) to kill cancer cells. However, its therapeutic effects are strictly confined by the short lifespan of OH and reduced OH generation speed. Herein, an effective CDT is achieved by both improving OH lifetime and long-lasting generating OH through intraparticle electron transfer within heterogeneous nanoparticles (NPs). These heterogeneous NPs are composed of evenly distributed Cu and FeO (CFO NPs) with large interaction interfaces, and electrons tend to transfer from Cu to FeO for the appearance of ≡Cu and increase in ≡Fe. The generated ≡Cu can interact with GSH, which prolongs the lifespan of OH, produces ≡Cu for higher speed OH generation with HO, and induces cell ferroptosis for tumor therapy. The improved ≡Fe can also improve the OH release under HO until Cu is depleted. As a result, a sustainable OH generation is achieved to promote cell apoptosis for effective tumor therapy. Since HO and GSH are only overexpressed at tumor, and CFO NPs can degrade in the tumor microenvironment, these NPs are with high biosafety and can be metabolized by urine. This work provides a novel biomaterial for effective cancer CDT through intraparticle electron transfer.
化学动力学疗法（CDT）是一种通过羟基自由基（OH）杀死癌细胞的新型肿瘤治疗方法。然而，其治疗效果受到 OH 寿命短和 OH 生成速度降低的严格限制。在此，通过在异质纳米颗粒（NPs）内的粒子内电子转移来提高 OH 的寿命和持续生成 OH，从而实现有效的 CDT。这些异质 NPs 由分布均匀的 Cu 和 FeO（CFO NPs）组成，具有较大的相互作用界面，电子倾向于从 Cu 转移到 FeO，从而出现≡Cu 并增加≡Fe。生成的≡Cu 可以与 GSH 相互作用，从而延长 OH 的寿命，与 HO 产生≡Cu 以实现更快的 OH 生成，并诱导细胞发生铁死亡以进行肿瘤治疗。改进的≡Fe 还可以在 HO 存在下提高 OH 的释放，直到 Cu 耗尽。因此，实现了可持续的 OH 生成，以促进细胞凋亡，从而实现有效的肿瘤治疗。由于 HO 和 GSH 仅在肿瘤中过度表达，并且 CFO NPs 可以在肿瘤微环境中降解，因此这些 NPs 具有很高的生物安全性，并可以通过尿液代谢。这项工作通过粒子内电子转移为有效的癌症 CDT 提供了一种新型生物材料。
