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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引用次数: 0

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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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.