化学
激进的
相扑蛋白
胶束
DNA
转录因子
生物物理学
两亲性
羟基自由基
癌症研究
组合化学
生物化学
基因
聚合物
有机化学
泛素
生物
水溶液
共聚物
作者
Peiran Zhao,Yong Li,Bingxia Sun,Chaochao Wang,Guanglei Lv,C. Chen,Leslie Ying,Xinhong He,Dayong Jin,Wenbo Bu
标识
DOI:10.1002/anie.202405913
摘要
Inactivating hyperactivated transcription factors can overcome tumor therapy resistance, but their undruggable features limit the development of conventional inhibitors. Here, we report that carbon‐centered free radicals (R∙) can inactivate NF‐κB transcription by capping the active sites in both NF‐κB and DNA. We construct a type of thermosensitive R∙ initiator loaded amphiphilic nano‐micelles to facilitate intracellular delivery of R∙. At a temperature of 43°C, the generated R∙ engage in electrophilic radical addition towards double bonds in nucleotide bases, and simultaneously cap the sulfhydryl residues in NF‐κB through radical chain reaction. As a result, both NF‐κB nuclear translocation and NF‐κB‐DNA binding are suppressed, leading to a remarkable NF‐κB inhibition of up to 94.1%. We have further applied R∙ micelles in a clinical radiofrequency ablation tumor therapy model, showing remarkable NF‐κB inactivation and consequently tumor metastasis inhibition. Radical capping strategy not only provides a method to solve the heat‐sink effect in clinic tumor hyperthermia, but also suggests a new perspective for controllable modification of biomacromolecules in cancer therapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI