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不同配体修饰的碲化镉量子点诱导线粒体毒性机制的光谱和显微镜研究

Spectroscopic and Microscopic Studies on the Mechanism of Mitochondrial Toxicity Induced by CdTe QDs Modified with Different Ligands.

作者信息

Lai Lu, Jin Jian-Cheng, Xu Zi-Qiang, Ge Yu-Shu, Jiang Feng-Lei, Liu Yi

机构信息

State Key Laboratory of Virology & Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecule Sciences, Wuhan University, Wuhan, 430072, People's Republic of China.

出版信息

J Membr Biol. 2015 Aug;248(4):727-40. doi: 10.1007/s00232-015-9785-x. Epub 2015 Mar 11.

DOI:10.1007/s00232-015-9785-x
PMID:25758230
Abstract

Quantum dots (QDs) are increasingly applied in sensing, drug delivery, biomedical imaging, electronics industries, etc. Consequently, it is urgently required to examine their potential threat to humans and the environment. In the present work, the toxicity of CdTe QDs with nearly identical maximum emission wavelength but modified with two different ligands (MPA and BSA) to mitochondria was investigated using flow cytometry, spectroscopic, and microscopic methods. The results showed that QDs induced mitochondrial permeability transition (MPT), which resulted in mitochondrial swelling, collapse of the membrane potential, inner membrane permeability to H(+) and K(+), the increase of membrane fluidity, depression of respiration, alterations of ultrastructure, and the release of cytochrome c. Furthermore, the protective effects of CsA and EDTA confirmed QDs might be able to induce MPT via a Ca(2+)-dependent domain. However, the difference between the influence of CdTe QDs and that of Cd(2+) on mitochondrial membrane fluidity indicated the release of Cd(2+) was not the sole reason that QDs induced mitochondrial dysfunction, which might be related to the nanoscale effect of QDs. Compared with MPA-CdTe QDs, BSA-CdTe QDs had a greater effect on the mitochondrial swelling, membrane fluidity, and permeabilization to H(+) and K(+) by mitochondrial inner membrane, which was caused the fact that BSA was more lipophilic than MPA. This study provides an important basis for understanding the mechanism of the toxicity of CdTe QDs to mitochondria, and valuable information for safe use of QDs in the future.

摘要

量子点(QDs)在传感、药物递送、生物医学成像、电子工业等领域的应用日益广泛。因此,迫切需要研究它们对人类和环境的潜在威胁。在本研究中,使用流式细胞术、光谱学和显微镜方法,研究了具有几乎相同的最大发射波长但用两种不同配体(MPA和BSA)修饰的CdTe量子点对线粒体的毒性。结果表明,量子点诱导线粒体通透性转换(MPT),导致线粒体肿胀、膜电位崩溃、内膜对H(+)和K(+)的通透性增加、膜流动性增加、呼吸抑制、超微结构改变以及细胞色素c的释放。此外,CsA和EDTA的保护作用证实量子点可能能够通过Ca(2+)依赖结构域诱导MPT。然而,CdTe量子点与Cd(2+)对线粒体膜流动性影响的差异表明,Cd(2+)的释放不是量子点诱导线粒体功能障碍的唯一原因,这可能与量子点的纳米效应有关。与MPA-CdTe量子点相比,BSA-CdTe量子点对线粒体肿胀、膜流动性以及线粒体内膜对H(+)和K(+)的通透性影响更大,这是因为BSA比MPA更具亲脂性。本研究为理解CdTe量子点对线粒体的毒性机制提供了重要依据,并为未来安全使用量子点提供了有价值的信息。

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