通过功能化 DNA 四面体的靶向诱导细胞内分解，可激活双癌症相关 RNA 成像和联合基因化疗,Analytical Chemistry

当前位置： X-MOL 学术 › Anal. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

通过功能化 DNA 四面体的靶向诱导细胞内分解，可激活双癌症相关 RNA 成像和联合基因化疗
Analytical Chemistry ( IF 6.7 ) Pub Date : 2022-04-05 , DOI: 10.1021/acs.analchem.2c00364
Ruichen Jia ₁ , Yitan Wang ₁ , Wenjie Ma ₁ , Jin Huang ₁ , Huanhuan Sun ₁ , Biao Chen ₁ , Hong Cheng ₁ , Xiaoxiao He ₁ , Kemin Wang ₁

Affiliation

不可否认，对同时具有准确诊断和有效治疗的癌症治疗系统的渴望是永无止境的。迄今为止，具有简单组件的治疗诊断系统被设计用于癌症治疗诊断，但诊断准确性和给药的副作用有限。在这里，我们报告了一种可激活的治疗诊断系统，用于同时成像双重癌症相关 RNA、mRNA Bcl-2 和 piRNA-36026，并通过靶诱导的 DNA 四面体的细胞内分解进行联合基因化疗。简而言之，五种定制的寡核苷酸用于组装功能化的 DNA 四面体。相关功能性核酸，包括 mRNA Bcl-2 的反序列、piRNA-36026 的反序列和适体 AS1411，设计在带有信号报告基因 Cy3 和 Cy5 的定制寡核苷酸中。阿霉素 (DOX) 通过嵌入胞嘧啶和鸟嘌呤之间的功能化 DNA 四面体中加载，形成可激活的癌症治疗系统。可激活的癌症治疗系统能够通过适配体 AS1411 识别 MCF-7 细胞，然后进入细胞。在靶标存在的情况下，可激活的癌症治疗系统中的反序列与细胞内 mRNA Bcl-2 和 piRNA-36026 杂交，导致 Cy3 和 Cy5 的荧光信号恢复和细胞质中两个靶标的下调以及随之而来的以基因治疗的形式凋亡MCF-7细胞。有趣的是，由于反序列是在组装链中设计的，靶标和反序列之间的杂交导致可激活的癌症治疗系统的分解和 DOX 的释放以及序贯化疗。有利的是，可激活的癌症治疗系统可以实现双癌相关RNA的成像，成像时间窗长达15小时，治疗效果明显。在体内。因此，这项工作将进一步探索高精度、高效率的可激活癌症治疗系统，为精准医学的发展提供新的思路。

"点击查看英文标题和摘要"

Activatable Dual Cancer-Related RNA Imaging and Combined Gene-Chemotherapy through the Target-Induced Intracellular Disassembly of Functionalized DNA Tetrahedron

The desire for a cancer theranostic system with simultaneously accurate diagnosis and efficient therapy is undeniably interminable. Heretofore, theranostic systems with simple components were designed for cancer theranostics but with confined accuracy of diagnosis and side effects of administered drugs. Here, we report an activatable theranostic system for simultaneously imaging dual cancer-related RNAs, mRNA Bcl-2 and piRNA-36026, and combined gene-chemotherapy through the target-induced intracellular disassembly of DNA tetrahedron. Briefly, five customized oligonucleotides are used to assemble the functionalized DNA tetrahedron. The relevant functional nucleic acids, including the antisequence of mRNA Bcl-2, the antisequence of piRNA-36026, and aptamer AS1411, are designed in the customized oligonucleotides with the signal reporters Cy3 and Cy5. Doxorubicin (DOX) is loaded in the functionalized DNA tetrahedron by inlaying between cytosine and guanine to form the activatable cancer theranostic system. The activatable cancer theranostic system is able to recognize MCF-7 cells by aptamer AS1411 and then enter the cells. In the presence of targets, the antisequences in the activatable cancer theranostic system hybridize with intracellular mRNA Bcl-2 and piRNA-36026, leading to the fluorescence signal recovery of Cy3 and Cy5 and the downregulation of two targets in the cytoplasm as well as the consequent apoptosis of MCF-7 cells in the form of gene therapy. Interestingly, as the antisequences are designed in the assembly strands, the hybridization between targets and the antisequences results in the disassembly of the activatable cancer theranostic system and the release of DOX as well as sequential chemotherapy. Advantageously, the activatable cancer theranostic system can achieve imaging of dual cancer-related RNAs with an imaging time window as long as 15 h and exhibit an obvious therapeutic effect in vivo. Therefore, this work is in furtherance of exploration for activatable cancer theranostic systems with high accuracy and efficiency and sheds new light on the development of precision medicine.

更新日期：2022-04-05

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南