Golubewa Lena, Kulahava Tatsiana, Timoshchenko Igor, Shuba Mikhail, Svirko Yuri, Kuzhir Polina
Department of Molecular Compounds Physics, State Research Institute Center for Physical Sciences and Technology, Saulėtekio av. 3, Vilnius, 10257, Lithuania.
Laboratory of Nanoelectromagnetics, Institute for Nuclear Problems of Belarusian State University, Bobruiskaya str. 11, Minsk, 220006, Belarus.
Nanotechnology. 2021 Oct 6;32(50). doi: 10.1088/1361-6528/ac28da.
Single-walled carbon nanotubes (SWCNTs) demonstrate a strong potential as an optically activated theranostic nano-agent. However, using SWCNTs in theranostics still requires revealing mechanisms of the SWCNT-mediated effects on cellular functions. Even though rapid and delayed cellular responses can differ significantly and may lead to undesirable consequences, understanding of these mechanisms is still incomplete. We demonstrate that introducing short (150-250 nm) SWCNTs into C6 rat glioma cells leads to SWCNT-driven effects that show pronounced time dependence. Accumulation of SWCNTs is carried out due to endocytosis with modification of the actin cytoskeleton but not accompanied with autophagy. Its initial stage launches a rapid cellular response via significantly heightened mitochondrial membrane potential and superoxide anion radical production, satisfying the cell demand of energy for SWCNT transfer inside the cytoplasm. In the long term, SWCNTs agglomerate to micron-sized structures surrounded by highly active mitochondria having parameters return to control values. SWCNTs postponed effects are also manifested themselves in the suppression of the cell proliferative activity with further restoration after five passages. These results demonstrate relative cellular inertness and safety of SWCNTs eliminating possible side effects caused by optically activated theranostic applications.
单壁碳纳米管（SWCNTs）作为一种光激活的诊疗纳米剂展现出强大的潜力。然而，在诊疗中使用SWCNTs仍需要揭示SWCNT介导的细胞功能效应机制。尽管快速和延迟的细胞反应可能有显著差异并可能导致不良后果，但对这些机制的理解仍不完整。我们证明，将短（150 - 250纳米）SWCNTs引入C6大鼠胶质瘤细胞会导致SWCNT驱动的效应呈现出明显的时间依赖性。SWCNTs的积累是通过肌动蛋白细胞骨架修饰的内吞作用进行的，但不伴有自噬。其初始阶段通过显著提高线粒体膜电位和超氧阴离子自由基生成引发快速细胞反应，满足细胞将SWCNT转运到细胞质内所需的能量。从长期来看，SWCNTs聚集成被高活性线粒体包围的微米级结构，其参数恢复到对照值。SWCNTs的延迟效应还表现为抑制细胞增殖活性，传代五次后进一步恢复。这些结果证明了SWCNTs相对细胞惰性和安全性，消除了光激活诊疗应用可能引起的副作用。
