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工程化DNA纳米孔:从结构演变到传感与运输

Engineering DNA nanopores: from structural evolution to sensing and transport.

作者信息

Liu Fengyu, Arai Tatsuo, Guo Dezhou, Jiang Zhuangde, Zhao Libo, Liu Xiaoming

机构信息

National Key Laboratory of Autonomous Intelligent Unmanned Systems, Beijing Institute of Technology, Beijing, 100081, China.

Key Laboratory of Biomimetic Robots and Systems (Ministry of Education), Beijing Institute of Technology, Beijing, 100081, China.

出版信息

Mater Today Bio. 2025 Jul 26;34:102137. doi: 10.1016/j.mtbio.2025.102137. eCollection 2025 Oct.

DOI:10.1016/j.mtbio.2025.102137
PMID:40761509
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12320668/
Abstract

Synthetic nanopores, inspired by natural ion channels and nuclear pore complexes, hold immense potential for elucidating cellular transport mechanisms and enhancing molecular sensing technologies. DNA nanotechnology, particularly DNA origami, stands out as a transformative platform for designing biomimetic nanopores, leveraging its biocompatibility, structural programmability, and mechanical tunability. This review traces the structural evolution of DNA nanopores across three phases: early hybrid designs with solid-state platforms, vertically-inserted nanopores in lipid bilayers, and horizontally-arranged nanopores with advanced functionalities. Unlike prior reviews, we integrate this progression with critical insights into limitations-such as stability, scalability, and noise-while highlighting breakthroughs in single-molecule sensing and controlled transmembrane transport. We conclude by outlining strategies for next-generation DNA nanopores, offering a roadmap for their optimization in synthetic biology and nanomedicine.

摘要

受天然离子通道和核孔复合体启发的合成纳米孔,在阐明细胞运输机制和增强分子传感技术方面具有巨大潜力。DNA纳米技术,尤其是DNA折纸术,凭借其生物相容性、结构可编程性和机械可调性,成为设计仿生纳米孔的变革性平台。本综述追溯了DNA纳米孔在三个阶段的结构演变:与固态平台的早期混合设计、脂质双层中垂直插入的纳米孔,以及具有先进功能的水平排列纳米孔。与以往的综述不同,我们将这一进展与对稳定性、可扩展性和噪声等局限性的关键见解相结合,同时突出单分子传感和受控跨膜运输方面的突破。我们通过概述下一代DNA纳米孔的策略来得出结论,为其在合成生物学和纳米医学中的优化提供路线图。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/9f99779ca603/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/fadfe7d63fd5/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/9f4b8ee64e54/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/358dbb17d6a8/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/6358dcc5458b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/e124f920a326/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/bcc5fa0e8d97/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/b06a1fc636fa/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/66dc33e22ae9/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/9f99779ca603/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/fadfe7d63fd5/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/9f4b8ee64e54/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/358dbb17d6a8/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/6358dcc5458b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/e124f920a326/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/bcc5fa0e8d97/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/b06a1fc636fa/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/66dc33e22ae9/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7958/12320668/9f99779ca603/gr8.jpg

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本文引用的文献

1
Elucidating the nanoscopic organization and dynamics of the nuclear pore complex.阐明核孔复合体的纳米级组织和动力学。
Nucleus. 2025 Dec;16(1):2510106. doi: 10.1080/19491034.2025.2510106. Epub 2025 Jun 4.
2
Predesigned DNA Origami Nanodrills Mediate Controlled Pore Formation on a Plasma Membrane and Cell Death.预设计的DNA折纸纳米钻介导质膜上的可控孔形成及细胞死亡。
Nano Lett. 2025 May 21;25(20):8220-8226. doi: 10.1021/acs.nanolett.5c01290. Epub 2025 May 9.
3
Specific ATP Detection Using Molecule-Responsive DNA Nanopores.
使用分子响应性DNA纳米孔进行特定ATP检测。
Small. 2025 May 2:e2409293. doi: 10.1002/smll.202409293.
4
Unraveling the time course of interaction between DNA nanopores and lipid bilayers using QCM-D: role of cholesterol anchors and bilayer supporting substrates.使用石英晶体微天平耗散技术(QCM-D)揭示DNA纳米孔与脂质双层之间相互作用的时间进程:胆固醇锚定和双层支撑底物的作用
Nanoscale. 2025 May 9;17(18):11668-11678. doi: 10.1039/d5nr01299f.
5
DNA Nanotubule-Based Nanodevices with ATP-Responsive Gating for Direct Cytosolic Delivery of Nucleic Acids and Proteins.基于DNA纳米管的纳米器件,具有ATP响应门控功能,用于核酸和蛋白质的直接胞质递送。
Angew Chem Int Ed Engl. 2025 Jun 10;64(24):e202505290. doi: 10.1002/anie.202505290. Epub 2025 Apr 16.
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Detection of protein oligomers with nanopores.利用纳米孔检测蛋白质寡聚体。
Nat Rev Chem. 2025 Apr;9(4):224-240. doi: 10.1038/s41570-025-00694-7. Epub 2025 Mar 5.
7
Rational design of a 3D DNA origami cube as an ideal signal carrier for glass nanopore-based biosensors.作为基于玻璃纳米孔的生物传感器的理想信号载体的三维DNA折纸立方体的合理设计。
Anal Chim Acta. 2025 Mar 15;1343:343660. doi: 10.1016/j.aca.2025.343660. Epub 2025 Jan 16.
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Curr Opin Chem Biol. 2025 Feb;84:102567. doi: 10.1016/j.cbpa.2024.102567. Epub 2024 Dec 31.
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Nano Lett. 2024 Oct 30;24(43):13481-13486. doi: 10.1021/acs.nanolett.4c02302. Epub 2024 Oct 21.