组会讲课人员:张筱斌
Ferroptosis-Enhanced Cancer Immunity by a Ferrocene-AppendedIridium(III) Diphosphine Complex
附加二茂铁的铱 (III) 二膦复合物可增强铁死亡的癌症免疫力
主讲人:张筱斌
Angewandte Chemie International Edition (IF 16.823) Pub Date : 2021-12-29 ,DOI:10.1002/anie.202115247
Abstract:
Ferroptosis is a programmed cell death pathway discovered in recent years, and ferroptosis-inducing agents have great potential as new antitumor candidates. Here, we report a IrIII complex (Ir1) containing a ferrocene-modified diphosphine ligand that localizes in lysosomes. Under the acidic environments of lysosomes, Ir1 can effectively catalyze Fenton-like reaction, produce hydroxyl radicals, induce lipid peroxidation, downregulate glutathione peroxidase 4, and result in ferroptosis. RNA sequencing analysis shows that Ir1 can significantly affect pathways related to ferroptosis and cancer immunity. Accordingly, Ir1 can induce immunogenic cells death and suppress tumor growth in vitro, regulate T cell activity and immune microenvironments in vivo. In conclusion, we show the potential of small molecules with ferroptosis-inducing capabilities for effective cancer immunotherapy.
摘要:
摘要:铁死亡是近年来发现的一种程序性细胞死亡途径,而铁死亡诱导剂作为新的抗肿瘤候选药物具有很大的潜力。在此,我们报道了一种IrIII 复合物(Ir1)含有二茂铁修饰的二膦配体,定位于溶酶体中。在溶酶体的酸性环境下,Ir1能有效催化芬顿样反应,产生羟基自由基,诱导脂质过氧化,下调谷胱甘肽过氧化物酶4,导致铁死亡。RNA测序分析显示,Ir1可以显著影响与铁死亡和癌症免疫相关的通路。据此,Ir1在体外可诱导免疫原性细胞死亡和抑制肿瘤生长,在体内可调节T细胞活性和免疫微环境。总之,我们展示了具有诱导铁脱铁能力的小分子在有效癌症免疫治疗方面的潜力。