Programming a DNA tetrahedral nanomachine as an integrative tool for intracellular microRNA biosensing and stimulus-unlocked target regulation.
Programming a DNA tetrahedral nanomachine as an integrative tool for intracellular microRNA biosensing and stimulus-unlocked target regulation.
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DOI：
10.1016/j.mtbio.2022.100276
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发表时间：
2022-06
影响因子：
8.2
通讯作者：
Chen, Ming
中科院分区：
文献类型：
--
作者：
Yu, Lianyu;Yang, Sha;Liu, Zeyu;Qiu, Xiaopei;Tang, Xiaoqi;Zhao, Shuang;Xu, Hanqing;Gao, Mingxuan;Bao, Jing;Zhang, Ligai;Luo, Dan;Chang, Kai;Chen, Ming
MicroRNAs(MiRNAs)的同步检测和调控对于肿瘤的早期诊断和治疗是必不可少的，但仍然是一个挑战。自组装了一体式DNA四面体纳米机器，用于对细胞内miRNAs的灵敏检测和负反馈调节。该纳米机器以DNA四面体纳米结构为骨架，以miRNA抑制剂控制的变构DNAzyme为核心。DNA四面体使DNAzyme和底物在空间上接近，促进细胞对DNAzyme的摄取。在DNAzyme的变构调节中，锁定的四面体DNAzyme(L-TETRA-D)和活性的四面体DNAzyme(A-TETRA-D)是由miRNA抑制剂控制的。MiRNA抑制剂与靶蛋白的联合作用可引发L-四-D向A-四-D的构象转变。A-Tetra-D裂解底物，释放荧光，用于细胞内miRNA生物传感。该DNA四面体纳米机器具有良好的灵敏度(检测下限为0.77 pm)、特异性(一碱基错配判别)、生物相容性和稳定性。同时，我们的纳米机器引入的miRNA刺激解锁抑制物表现出对靶细胞的同步调节，其调节性能已被下游基因/蛋白质水平上调和细胞凋亡增加所验证。我们的研究表明，DNA四面体纳米机器是一种有前景的生物传感和治疗工具，用于同步检测和调节细胞内miRNA，并有望应用于癌症的早期诊断和量身定制的治疗。设计了一种集成DNA四面体纳米机器的生物传感和治疗平台，用于同时灵敏地检测和负反馈调节细胞内microRNAs(MiRNAs)。
The synchronous detection and regulation of microRNAs (miRNAs) are essential for the early tumor diagnosis and treatment but remains a challenge. An integrative DNA tetrahedral nanomachine was self-assembled for sensitive detection and negative feedback regulation of intracellular miRNAs. This nanomachine comprised a DNA tetrahedron nanostructure as the framework, and a miRNA inhibitor-controlled allosteric DNAzyme as the core. The DNA tetrahedron brought the DNAzyme and the substrate in spatial proximity and facilitated the cellular uptake of DNAzyme. In allosteric regulation of DNAzyme, the locked tetrahedral DNAzyme (L-tetra-D) and active tetrahedral DNAzyme (A-Tetra-D) were controlled by miRNA inhibitor. The combination of miRNA inhibitor and target could trigger the conformational change from L-tetra-D to A-Tetra-D. A-Tetra-D cleaved the substrate and released fluorescence for intracellular miRNA biosensing. The DNA tetrahedral nanomachine showed excellent sensitivity (with detection limit down to 0.77 pM), specificity (with one-base mismatch discrimination), biocompatibility and stability. Simultaneously, miRNA stimulus-unlocked inhibitor introduced by our nanomachine exhibited the synchronous regulation of target cells, of which regulatory performance has been verified by the upregulated levels of downstream genes/proteins and the increased cellular apoptosis. Our study demonstrated that the DNA tetrahedral nanomachine is a promising biosense-and-treat tool for the synchronous detection and regulation of intracellular miRNA, and is expected to be applied in the early diagnosis and tailored management of cancers. An integrative DNA tetrahedral nanomachine, a biosense-and-treat platform was programmed for the simultaneous sensitive detection and negative feedback regulation of intracellular microRNAs (miRNAs).
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影响因子：
6.1
作者：
Hosseinzadeh, Elyas;Ravan, Hadi;Pourghadamyari, Hossein
通讯作者：
Pourghadamyari, Hossein
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影响因子：
17.1
作者：
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Tan, Weihong
影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
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作者：
BREAKER, RR;JOYCE, GF
通讯作者：
JOYCE, GF
催化 DNA 分子尺度检测器的定向四面体介导保护，防止细胞内 miRNA 检测的体内降解
影响因子：
7.4
作者：
Li, Congcong;Xue, Chang;Wu, Zai-Sheng
通讯作者：
Wu, Zai-Sheng