Multivalence-Actuated DNA Nanomachines Enable Bicolor Exosomal Phenotyping and PD-L1-Guided Therapy Monitoring
Multivalence-Actuated DNA Nanomachines Enable Bicolor Exosomal Phenotyping and PD-L1-Guided Therapy Monitoring
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多价驱动 DNA 纳米机器实现双色外泌体表型分析和 PD-L1 引导治疗监测
DOI：
10.1021/acs.analchem.0c01387
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发表时间：
2020-07-21
影响因子：
7.4
通讯作者：
Yang, Fan
中科院分区：
文献类型：
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作者：
Jin, Dan;Peng, Xin-Xin;Yang, Fan
外切体相关的液体活检受到外切体定量和表型鉴定方面的挑战的阻碍。在这里，我们提出了一种具有生物灵感的外切体激活的DNA分子机器(ExoADM)，它具有多价循环扩增功能，能够对循环外切体进行高灵敏度的检测和表型鉴定。ExoADM含有两个DNA脚趾结构域(一个暴露的和一个隐藏的)，它们启动顺序的分支迁移和响应胞外体表面标记的多价回收。重要的是，这种自供电的ExoADM实现了高灵敏度(33个颗粒/亩L)，并与另一台针对不同外体表面标记的DNA纳米机器兼容，用于双色表型。利用这一策略，我们可以同时跟踪信号分子诱导的ExoPD-L1和ExoCD63表达的动态变化。此外，我们发现它们在循环外切体上的表达水平可以很好地区分癌症患者和正常个体。更重要的是，ExoPD-L1水平可以反映不同治疗方案的疗效，指导抗PD-1免疫治疗，提示ExoPD-L1在临床诊断和靶向治疗监测方面的潜力。
Exosome-associated liquid biopsies are hampered by challenges in the exosomal quantification and phenotyping. Here, we present a bioinspired exosome-activated DNA molecular machine (ExoADM) with multivalent cyclic amplification that enables highly sensitive detection and phenotyping of circulating exosomes. ExoADM harbors two (an exposed and a hidden) DNA toehold domains that actuate sequential branch migration and multivalent recycling in response to exosomal surface markers. Importantly, this self-powered ExoADM achieves a high sensitivity (33 particles/mu L) and is compatible with another DNA nanomachine targeting different exosomal surface markers for dual-color phenotyping. Using this strategy, we can simultaneously track the dynamic changes of ExoPD-L1 and ExoCD63 expression induced by signaling molecules. Further, we found that their expression levels on circulating exosomes could well differentiate cancer patients from the normal individuals. More importantly, ExoPD-L1 levels could reflect the efficacy of different treatments and guide anti-PD-1 immunotherapy, suggesting the potential of ExoPD-L1 in clinical diagnosis and targeted therapy monitoring.