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聚合物包覆量子点的细胞毒性作用及其对活细胞应用的限制。

The cytotoxic effects of polymer-coated quantum dots and restrictions for live cell applications.

机构信息

Lab of General Biochemistry and Physical Pharmacy, Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium.

出版信息

Biomaterials. 2012 Jun;33(19):4882-8. doi: 10.1016/j.biomaterials.2012.03.042. Epub 2012 Apr 9.

Abstract

The interest in the biomedical use of highly fluorescent and photostable nanoparticles such as quantum dots (QDots) is vastly increasing. One major hurdle that impedes QDot use in live cells and animals is their potential toxicity. Here, we employ a recently described multiparametric setup to determine the concentration at which common polymer-coated QDots become non-cytotoxic. We found that toxic effects are strongly related to the intracellular QDot amount that can be controlled by their specific surface coating. Using lysosomal buffer systems and proliferation-restricted cells, intracellular QDots were found to localize in endosomes, where they generate reactive oxygen species, interfere with cell cytoskeleton and leach free Cd(2+) ions due to QDot dissolution, resulting in increased toxicity and impeded QDot fluorescence. Furthermore, we find that asymmetric partitioning of QDots upon recurrent cell division results in the sacrifice of heavily-loaded cells and a rapid loss of particles in live cells, limiting the use of currently available QDots for long-term imaging and defining the non-cytotoxic concentration as 10-fold lower than commonly used concentrations.

摘要

人们对高度荧光和光稳定性的纳米粒子(如量子点)在生物医学中的应用越来越感兴趣。阻碍量子点在活细胞和动物中应用的一个主要障碍是其潜在的毒性。在这里,我们采用了最近描述的多参数设置来确定常见聚合物涂层量子点变得无毒的浓度。我们发现,毒性效应与细胞内量子点的数量密切相关,而细胞内量子点的数量可以通过其特定的表面涂层来控制。使用溶酶体缓冲系统和增殖受限的细胞,我们发现细胞内量子点定位于内体中,在那里它们产生活性氧,干扰细胞细胞骨架,并由于量子点的溶解而漏出游离的 Cd(2+)离子,导致毒性增加和量子点荧光减弱。此外,我们发现,由于反复的细胞分裂导致量子点的不对称分配,从而导致负载较重的细胞牺牲,以及活细胞中粒子的快速损失,限制了目前可用的量子点在长期成像中的应用,并将非细胞毒性浓度定义为比常用浓度低 10 倍。

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