Key Laboratory of Environmental Medicine & Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, PR China.
Key Laboratory of Environmental Medicine & Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, PR China.
NanoImpact. 2022 Jan;25:100367. doi: 10.1016/j.impact.2021.100367. Epub 2021 Nov 26.
Despite the potential of cadmium telluride quantum dots (CdTe QDs) in bioimaging and drug delivery, their toxic effects have been documented. It is known that the immunotoxicity of CdTe QDs targeting macrophages is one of their adverse effects, and the protein corona (PC) will affect the biological effects of QDs. In order to prove whether the PC-CdTe QDs complexes could alleviate the toxicity of CdTe QDs without weakening their luminescence, we investigated the impact of protein corona formed in fetal bovine serum (FBS) on the cytotoxicity of CdTe QDs to mitochondria. RAW264.7 cells were used as the model to compare the effects of CdTe QDs and PC-CdTe QDs complexes on the structure, function, quantity, morphology, and mitochondrial quality control of mitochondria. As result, the protein corona form in FBS alleviated the inhibition of CdTe QDs on mitochondrial activity, the damage to mitochondrial membrane, the increase of ROS, and the reduction of ATP content. Also, CdTe QDs increased the number of mitochondria in macrophages, while the complexes did not. In line with this, the morphology of mitochondrial network in macrophages which were exposed to CdTe QDs and PC-CdTe QDs complexes was different. CdTe QDs transformed the network into fragments, punctuations, and short rods, while PC-CdTe QDs complexes made the mitochondrial network highly branched, which was related to the imbalance of mitochondrial fission and fusion. Mechanically, CdTe QDs facilitated mitochondrial fission and inhibited mitochondrial fusion, while protein corona reversed the phenomenon caused by QDs. Besides mitochondrial dynamics, mitochondrial biogenesis and mitophagy were also affected. CdTe QDs increased the expression of mitochondrial biogenesis signaling molecules including PGC-1α, NRF-1 and TFAM, while PC-CdTe QDs complexes played the opposite role. With regard to mitophagy, they both showed promoting effect. In conclusion, the formation of protein corona alleviated the toxic effects of CdTe QDs on the mitochondria in macrophages and affected mitochondrial quality control. Under the premise of ensuring the fluorescence properties of CdTe QDs, these findings provided useful insight into reducing the toxicity of CdTe QDs from two perspectives: protein corona and mitochondria, and shared valuable information for the safe use of QDs.
尽管碲化镉量子点（CdTe QDs）在生物成像和药物输送方面具有潜力，但它们的毒性作用已被记录在案。已知 CdTe QDs 靶向巨噬细胞的免疫毒性是其不良影响之一，而蛋白质冠（PC）会影响 QDs 的生物学效应。为了证明 PC-CdTe QDs 复合物是否可以减轻 CdTe QDs 的毒性而不减弱其发光，我们研究了胎牛血清（FBS）中形成的蛋白质冠对 CdTe QDs 对线粒体细胞毒性的影响。RAW264.7 细胞被用作模型，比较了 CdTe QDs 和 PC-CdTe QDs 复合物对线粒体结构、功能、数量、形态和线粒体质量控制的影响。结果表明，FBS 中形成的蛋白质冠减轻了 CdTe QDs 对线粒体活性的抑制、线粒体膜的损伤、ROS 的增加和 ATP 含量的减少。此外，CdTe QDs 增加了巨噬细胞中线粒体的数量，而复合物则没有。与此一致的是，暴露于 CdTe QDs 和 PC-CdTe QDs 复合物的巨噬细胞中线粒体网络的形态也不同。CdTe QDs 将网络转化为片段、斑点和短棒，而 PC-CdTe QDs 复合物使线粒体网络高度分支，这与线粒体分裂和融合的失衡有关。从机械上讲，CdTe QDs 促进了线粒体分裂并抑制了线粒体融合，而蛋白质冠则逆转了 QDs 引起的现象。除了线粒体动力学之外，线粒体生物发生和噬线粒体也受到影响。CdTe QDs 增加了线粒体生物发生信号分子的表达，包括 PGC-1α、NRF-1 和 TFAM，而 PC-CdTe QDs 复合物则起到相反的作用。关于噬线粒体，它们都表现出促进作用。总之，蛋白质冠的形成减轻了 CdTe QDs 对巨噬细胞中线粒体的毒性作用，并影响了线粒体的质量控制。在确保 CdTe QDs 荧光特性的前提下，这些发现从蛋白质冠和线粒体两个角度为降低 CdTe QDs 的毒性提供了有用的见解，并为 QDs 的安全使用提供了有价值的信息。
