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湖南大學(xué)譚蔚泓院士課題組在Nano Letters 發(fā)文采用我司Si-IDA-Ni磁珠結(jié)合His標(biāo)簽蛋白

DNA Nanostructure-Programmed Cell Entry via Corner Angle-Mediated Molecular Interaction with Membrane Receptors

Xueyu Peng, Senbiao Fang, Bin Ji, Min Li, Jie Song, Liping Qiu*, and Weihong Tan*
Nano Letters  2021, 21, 16, 6946-6951 (Letter)Subscribed Access
Publication Date (Web):August 16, 2021

DOI: 10.1021/acs.nanolett.1c02191

Despite its polyanionic nature, DNA can cross the negatively charged membrane to enter living cells by assembling into specific nanostructures, establishing various opportunities for biomedical applications. Mechanistic studies to explain how the geometrical parameters of DNA nanostructures impact the cell entry are critical but elusive. Here, we use experimentation and simulation to study the interaction between cells and three typical framework nucleic acids (FNAs), including tetrahedron, triangular prism, and cube. Different cellular uptake efficiency was observed among these FNAs, and similar distinction consistently existed in multiple cell lines. Scavenger receptors (SRs) were demonstrated to be essential in mediating the uptake process. Molecular docking simulations revealed that the SR binding predominantly depended on the corner angle of FNAs, determining cellular internalization frequency. This study clearly explains how FNAs interact with the membrane to initiate cell entry, offering new clues for the design of theranostic nanocarriers and the study of virus invasion.

盡管具有多陰離子性質(zhì)，但 DNA 可以通過組裝成特定的納米結(jié)構(gòu)穿過帶負(fù)電荷的膜進(jìn)入活細(xì)胞，從而為生物醫(yī)學(xué)應(yīng)用創(chuàng)造各種機(jī)會(huì)。解釋 DNA 納米結(jié)構(gòu)的幾何參數(shù)如何影響細(xì)胞進(jìn)入的機(jī)制研究至關(guān)重要，但難以捉摸。在這里，我們使用實(shí)驗(yàn)和模擬來研究細(xì)胞與三種典型框架核酸 (FNA) 之間的相互作用，包括四面體、三棱柱和立方體。在這些 FNA 中觀察到不同的細(xì)胞攝取效率，并且在多個(gè)細(xì)胞系中始終存在類似的區(qū)別。清道夫受體 (SRs) 被證明在介導(dǎo)攝取過程中是必不可少的。分子對(duì)接模擬顯示，SR 結(jié)合主要取決于 FNA 的角角，決定了細(xì)胞內(nèi)化頻率。這項(xiàng)研究清楚地解釋了 FNA 如何與膜相互作用以啟動(dòng)細(xì)胞進(jìn)入，為治療診斷納米載體的設(shè)計(jì)和病毒入侵的研究提供了新的線索。

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