The Straits Institute of Flexible Electronics (SIFE, Future Technologies), The Straits Laboratory of Flexible Electronics (SLoFE), Fujian Normal University, Fuzhou, Fujian, 350117, China.
Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, 1 Keji Road, Fuzhou, 350117, PR China.
J Nanobiotechnology. 2024 May 8;22(1):228. doi: 10.1186/s12951-024-02508-2.
Development of ferroptosis-inducible nanoplatforms with high efficiency and specificity is highly needed and challenging in tumor ferrotherapy. Here, we demonstrate highly effective tumor ferrotherapy using iron (II)-based metal-organic framework (FessMOF) nanoparticles, assembled from disulfide bonds and ferrous ions. The as-prepared FessMOF nanoparticles exhibit peroxidase-like activity and pH/glutathione-dependent degradability, which enables tumor-responsive catalytic therapy and glutathione depletion by the thiol/disulfide exchange to suppress glutathione peroxidase 4, respectively. Upon PEGylation and Actinomycin D (ActD) loading, the resulting FessMOF/ActD-PEG nanoplatform induces marked DNA damage and lipid peroxidation. Concurrently, we found that ActD can inhibit Xc system and elicit ferritinophagy, which further boosts the ferrotherapeutic efficacy of the FessMOF/ActD-PEG. In vivo experiments demonstrate that our fabricated nanoplatform presents excellent biocompatibility and a high tumor inhibition rate of 91.89%.
高效和特异性的铁死亡诱导纳米平台的开发在肿瘤铁疗中是非常需要和具有挑战性的。在这里，我们展示了使用由二硫键和亚铁离子组装而成的铁(II)基金属有机骨架（FessMOF）纳米颗粒进行高效的肿瘤铁疗。所制备的 FessMOF 纳米颗粒具有过氧化物酶样活性和 pH/谷胱甘肽依赖性降解性，分别通过硫醇/二硫键交换实现肿瘤响应性催化治疗和谷胱甘肽耗竭，以抑制谷胱甘肽过氧化物酶 4。经过聚乙二醇化和 Actinomycin D（ActD）负载后，所得的 FessMOF/ActD-PEG 纳米平台会引起明显的 DNA 损伤和脂质过氧化。同时，我们发现 ActD 可以抑制 Xc 系统并引发铁蛋白自噬，这进一步增强了 FessMOF/ActD-PEG 的铁疗效果。体内实验表明，我们制备的纳米平台具有良好的生物相容性和高达 91.89%的肿瘤抑制率。
