College of Chemistry, Chemical Engineering, and Materials Science, Soochow University, Suzhou 215123, China.
NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Molecules. 2024 May 24;29(11):2495. doi: 10.3390/molecules29112495.
Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeCl(TMPPH)][FeCl] () exhibits a superior anticancer performance on a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC) values in the range of 0.098-3.97 μM (0.066-2.68 μg mL), comparable to the best-reported medicines. can form stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed HO, converting HO to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells.
开发用于癌症治疗的具有临床意义的纳米药物需要药物具有有效性、安全性、简单性、廉价性和易于储存性。在本工作中，我们报道了一种简单的阳离子富铁[FeCl(TMPPH)][FeCl]（）盐在广谱的癌细胞系中表现出优异的抗癌性能，包括乳腺癌、结直肠癌、肝癌、胰腺癌、前列腺癌和胃癌，其半最大抑制浓度（IC）值在 0.098-3.97 μM（0.066-2.68 μg mL）范围内，可与报道最好的药物相媲美。可以在水中形成独立的纳米颗粒，无需额外的表面修饰或有机溶剂辅助反溶剂沉淀。关键的是，对肿瘤微环境（TME）有响应，并且只有在 TME 中过表达 HO 时才能发挥其功能，将 HO 转化为细胞毒性的•OH 来氧化癌细胞膜的磷脂，导致铁死亡，这是一种癌细胞程序性死亡过程。
