Folding an RCA Scaffold into an Intelligent Coiled Nanosnake for Precise/Synergistic RNAi-/Chemotherapy of Cancer

IF 6.7 1区化学 Q1 CHEMISTRY, ANALYTICAL Analytical Chemistry Pub Date : 2025-01-09 DOI:10.1021/acs.analchem.4c03437

Congcong Li, Wenqing Lin, Weijun Wang, Jingting Wu, Shasha Luo, Linhuan Chen, Rong Wu, Zhifa Shen, Zai-Sheng Wu

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Abstract

An RCA product is a promising scaffold for the construction of DNA nanostructures, but so far, there is no RCA scaffold-based dynamic reconfigurable nanorobot for biological applications. In this contribution, we develop an intracellular stimuli-responsive reconfigurable coiled DNA nanosnake (N-Snake) by using incomplete aptamer-functionalized (A) DNA tetrahedrons (T) to fold a long tandemly repetitive DNA strand synthesized by rolling circle amplification reaction (R) with the help of palindromic fragment (P). A DNA-assembled product, ARTP, including spiked aptamers, can retain the structural integrity even if exposed to fetal bovine serum (FBS) for 24 h and displays substantially enhanced target molecule-dependent cellular internalization efficiency. ARTP contains tetrahedral containers and linear containers, so that there are 500 doxorubicins (DOXs) and 12.5 siRNAs per ARTP. Moreover, ARTP can precisely transport anticancer drugs to cancerous sites and controllably release via the structural reconfiguration upon intracellular stimuli, almost 100% inhibiting tumor growth without detectable systemic toxicity owing to the synergistic RNAi-/Chemotherapy. Apparently, coiled N-snake, DOX/siPlk1-loaded ARTP, can specifically enter tumor cells, uncoil upon intracellular stimuli, and attack the cells from the inside, exerting precise cancer therapy.

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将RCA支架折叠成智能卷曲纳米蛇用于精确/协同RNAi /癌症化疗

RCA产品是一种很有前途的DNA纳米结构构建支架，但目前还没有基于RCA支架的生物动态可重构纳米机器人。在这篇文章中，我们利用不完全适配体功能化(A) DNA四面体(T)折叠由回文片段(P)的滚动圈扩增反应(R)合成的长串重复DNA链，开发了一种细胞内刺激响应的可重构卷曲DNA纳米蛇（N-Snake）。即使暴露于胎牛血清（FBS） 24小时，也能保持结构完整性，并显示出显著增强的靶分子依赖性细胞内化效率。ARTP包含四面体容器和线性容器，因此每个ARTP有500个阿霉素（DOXs）和12.5个sirna。此外，由于RNAi-/化疗的协同作用，ARTP可以精确地将抗癌药物转运到癌症部位，并在细胞内刺激下通过结构重组可控地释放，几乎100%抑制肿瘤生长，而没有可检测到的全身毒性。显然，盘绕的N-snake， DOX/ siplk1负载的ARTP，可以特异性地进入肿瘤细胞，在细胞内刺激下展开，并从细胞内部攻击细胞，发挥精确的癌症治疗作用。

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来源期刊

Analytical Chemistry 化学-分析化学

CiteScore

12.10

自引率

12.20%

发文量

1949

审稿时长

1.4 months

期刊介绍： Analytical Chemistry, a peer-reviewed research journal, focuses on disseminating new and original knowledge across all branches of analytical chemistry. Fundamental articles may explore general principles of chemical measurement science and need not directly address existing or potential analytical methodology. They can be entirely theoretical or report experimental results. Contributions may cover various phases of analytical operations, including sampling, bioanalysis, electrochemistry, mass spectrometry, microscale and nanoscale systems, environmental analysis, separations, spectroscopy, chemical reactions and selectivity, instrumentation, imaging, surface analysis, and data processing. Papers discussing known analytical methods should present a significant, original application of the method, a notable improvement, or results on an important analyte.