三聚体
DNA折纸
DNA
细胞凋亡
化学
受体
配体(生物化学)
单体
程序性细胞死亡
DNA损伤
生物物理学
纳米技术
癌细胞
细胞毒性
聚类分析
细胞生物学
二聚体
癌症
生物化学
体外
生物
材料科学
遗传学
计算机科学
聚合物
有机化学
机器学习
作者
Nana Ma,Keman Cheng,Qingqing Feng,Guangna Liu,Jie Liang,Xiaotu Ma,Zhiqiang Chen,Yichao Lu,Xinwei Wang,Wei He,Hu Xu,Shan Wu,Jiajia Zou,Quanwei Shi,Guangjun Nie,Xiao Zhao
出处
期刊:Small
[Wiley]
日期:2023-03-08
卷期号:19 (23)
被引量:11
标识
DOI:10.1002/smll.202206160
摘要
Abstract Through inducing death receptor (DR) clustering to activate downstream signaling, tumor necrosis factor related apoptosis inducing ligand (TRAIL) trimers trigger apoptosis of tumor cells. However, the poor agonistic activity of current TRAIL‐based therapeutics limits their antitumor efficiency. The nanoscale spatial organization of TRAIL trimers at different interligand distances is still challenging, which is essential for the understanding of interaction pattern between TRAIL and DR. In this study, a flat rectangular DNA origami is employed as display scaffold, and an “engraving‐printing” strategy is developed to rapidly decorate three TRAIL monomers onto its surface to form DNA‐TRAIL3 trimer (DNA origami with surface decoration of three TRAIL monomers). With the spatial addressability of DNA origami, the interligand distances are precisely controlled from 15 to 60 nm. Through comparing the receptor affinity, agonistic activity and cytotoxicity of these DNA‐TRAIL3 trimers, it is found that ≈40 nm is the critical interligand distance of DNA‐TRAIL3 trimers to induce death receptor clustering and the resulting apoptosis.Finally, a hypothetical “active unit” model is proposed for the DR5 clustering induced by DNA‐TRAIL3 trimers.
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