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基于多功能控制释放机制的用于多重遗传毒性物质检测的工程化多价 DNA 胶囊。

Engineered multivalent DNA capsules for multiplexed detection of genotoxicants via versatile controlled release mechanisms.

机构信息

Department of Chemistry, Tunghai University, Taichung, 407224, Taiwan.

Institute of Population Health Sciences, National Health Research Institutes, Miaoli, 35053, Taiwan.

出版信息

Biosens Bioelectron. 2022 Nov 15;216:114608. doi: 10.1016/j.bios.2022.114608. Epub 2022 Aug 5.

DOI:10.1016/j.bios.2022.114608
PMID:35961122
Abstract

Assessing the risks associated with genotoxic compounds is challenging because of their complex genotoxicity and the difficulty in the dynamic monitoring of coexisting hazards. In this paper, DNA-assembly-based multistimulus responsive capsules that can detect multiple genotoxic agents simultaneously are presented. By exploiting the sequence- and reactivity-editable properties of DNA, DNA sequences in a DNA shell are designed to exhibit multivalent susceptibility against ultraviolet B radiation, aflatoxin B1, and styrene oxide. Upon exposure to genotoxicants, the developed DNA capsules dissociate because of the production of DNA adducts or aptamer-ligand complex-activated dehybridization, which results in the release of encapsulated fluorophores for a measure of the genotoxicant level. The fluorophore release kinetics for each genotoxicant is investigated. Moreover, the destruction behaviors of the developed capsules are evaluated in binary and ternary toxin mixtures. Multiple linear regression indicates the existence of a strong relationship between the fluorescent response and the genotoxicant level; the result highlights the significance of particular genotoxicant and the antagonistic effect of interacting genotoxic substances on capsule destruction. This DNA architecture allows the monitoring of human exposure to genotoxic agents, which enables the timely adoption of remedial measures, and benefits development of an endogenous genotoxin-responsive drug delivery system.

摘要

评估与遗传毒性化合物相关的风险具有挑战性,因为它们具有复杂的遗传毒性,并且难以对共存危害进行动态监测。在本文中,我们提出了一种基于 DNA 组装的多刺激响应胶囊,该胶囊可以同时检测多种遗传毒性剂。通过利用 DNA 的序列和反应性可编辑特性,设计 DNA 壳中的 DNA 序列对紫外线 B 辐射、黄曲霉毒素 B1 和苯乙烯氧化物表现出多价敏感性。在暴露于遗传毒性剂后,由于 DNA 加合物的产生或适体-配体复合物激活的解杂交,开发的 DNA 胶囊会解离,导致封装的荧光团释放,以测量遗传毒性剂水平。研究了每种遗传毒性剂的荧光团释放动力学。此外,还评估了开发的胶囊在二元和三元毒素混合物中的破坏行为。多元线性回归表明荧光响应与遗传毒性剂水平之间存在很强的关系;该结果突出了特定遗传毒性剂的重要性以及相互作用的遗传毒性物质对胶囊破坏的拮抗作用。这种 DNA 结构允许监测人类暴露于遗传毒性剂,从而能够及时采取补救措施,并有利于开发内源性遗传毒性反应性药物输送系统。

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