Modular Assembly of a Concatenated DNA Circuit for In Vivo Amplified Aptasensing
Modular Assembly of a Concatenated DNA Circuit for In Vivo Amplified Aptasensing
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用于体内放大适体传感的串联 DNA 电路的模块化组装
DOI：
10.1002/smll.202200983
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发表时间：
2022
期刊：
影响因子：
13.3
通讯作者：
Fuan Wang
中科院分区：
文献类型：
--
作者：
Qiong Wu;Lei Yang;Lingling Xie;Jinhua Shang;Shizhen He;Jing Liu;Fuan Wang
探索生物体内内源性分子谱对于阐明生物学功能和开发新的治疗诊断学具有重要意义。尽管在分子成像的广度上存在可编程的基于核酸的适体传感系统，但是高度需要能够以高灵敏度、准确度和适应性进行体内成像的适体传感系统，但该系统仍处于起步阶段。人工催化DNA电路可以模块化集成，以等温自主方式从单个输入产生多个输出，补充了细胞内生物传感研究的强大工具包。本文中，设计了一种基于多层非酶催化DNA电路的适体传感系统，用于通过基于雪崩模拟杂交链反应（HCR）组装具有高分子量和高信号增益的支链DNA共聚物来在活体小鼠中原位成像生物活性分子。HCRs适体传感电路由于其固有的丰富识别库和分级反应加速而作为通用和强大的传感平台用于精确分析一系列生物活性分子。通过肿瘤靶向胶囊封装，HCRs适配电路被特异性地递送到肿瘤细胞中，并允许活小鼠中细胞内三磷酸腺苷的高对比度成像，突出了其可视化这些临床重要生物分子和研究相关生理过程的潜力。
Probing endogenous molecular profiles in living entities is of fundamental significance to decipher biological functions and exploit novel theranostics. Despite programmable nucleic acid-based aptasensing systems across the breadth of molecular imaging, an aptasensing system enabling in vivo imaging with high sensitivity, accuracy, and adaptability is highly required yet is still in its infancy. Artificial catalytic DNA circuits that can modularly integrate to generate multiple outputs from a single input in an isothermal autonomous manner, have supplemented powerful toolkits for intracellular biosensing research. Herein, a multilayer nonenzymatic catalytic DNA circuits-based aptasensing system is devised for in situ imaging of a bioactive molecule in living mice by assembling branched DNA copolymers with high-molecular-weight and high-signal-gain based on avalanche-mimicking hybridization chain reactions (HCRs). The HCRs aptasensing circuit performs as a general and powerful sensing platform for precise analysis of a series of bioactive molecules due to its inherent rich recognition repertoire and hierarchical reaction accelerations. With tumor-targeting capsule encapsulation, the HCRs aptasensing circuit is specifically delivered into tumor cells and allowed the high-contrast imaging of intracellular adenosine triphosphate in living mice, highlighting its potential for visualizing these clinically important biomolecules and for studying the associated physiological processes.