Structure-tuned membrane active Ir-complexed oligoarginine overcomes cancer cell drug resistance and triggers immune responses in mice
Shuangshuang Ji, Xiuzhu Yang, Xiaolong Chen, Ang Li, Doudou Yan, Haiyan Xu, Fei Hao
Abstract
, hydrophobicity, topology and cationicity, on the regulation of the cytotoxicity of the Ir(iii)-oligoarginine peptides. With the most prominent toxicities, Ir-complexed octaarginines (R8) were found to display a progressive oncotic cell death featuring cell membrane-penetration and eruptive cytoplasmic content release. Consequently, this membrane-centric death mechanism showed promising potential in overcoming multiple chemical drug-resistance of cancer cells. More interestingly, the eruptive mode of cell death proved to be immunogenic by stimulating the dendritic cell maturation and inflammatory factor accumulation in mice tumours. Taking these mechanisms together, this work demonstrates that membrane active compounds may become the next generation chemotherapeutics because of their combined advantages.