Regional Centre of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute (CATRIN), Palacký University Olomouc, Křížkovského 511/8, 779 00 Olomouc, Czech Republic.
Laboratory of Biophysics, Condensed Matter Physics Department, Jožef Stefan Institute, Jamova Cesta 39, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2022 Jan 19;23(3):1077. doi: 10.3390/ijms23031077.
Fluorescent carbon dots (CDs) are potential tools for the labeling of cells with many advantages such as photostability, multicolor emission, small size, rapid uptake, biocompatibility, and easy preparation. Affinity towards organelles can be influenced by the surface properties of CDs which affect the interaction with the cell and cytoplasmic distribution. Organelle targeting by carbon dots is promising for anticancer treatment; thus, intracellular trafficking and cytotoxicity of cationic CDs was investigated. Based on our previous study, we used quaternized carbon dots (QCDs) for treatment and monitoring the behavior of two human cancer cell MCF-7 and HeLa lines. We found similarities between human cancer cells and mouse fibroblasts in the case of QCDs uptake. Time lapse microscopy of QCDs-labeled MCF-7 cells showed that cells are dying during the first two hours, faster at lower doses than at higher ones. QCDs at a concentration of 100 µg/mL entered into the nucleus before cellular death; however, at a dose of 200 µg/mL, blebbing of the cellular membrane occurred, with a subsequent penetration of QCDs into the nuclear area. In the case of HeLa cells, the dose-depended effect did not happen; however, the labeled cells were also dying in mitosis and genotoxicity occurred nearly at all doses. Moreover, contrasted intracellular compartments, probably mitochondria, were obvious after 24 h incubation with 100 µg/mL of QCDs. The levels of reactive oxygen species (ROS) slightly increased after 24 h, depending on the concentration, thus the genotoxicity was likely evoked by the nanomaterial. A decrease in viability did not reach IC 50 as the DNA damage was probably partly repaired in the prolonged G0/G1 phase of the cell cycle. Thus, the defects in the G2/M phase may have allowed a damaged cell to enter mitosis and undergo apoptosis. The anticancer effect in both cell lines was manifested mainly through genotoxicity.
荧光碳点（CDs）是细胞标记的潜在工具，具有许多优点，如光稳定性、多色发射、尺寸小、摄取快、生物相容性和易于制备。CDs 的表面性质可以影响其对细胞器的亲和力，从而影响与细胞的相互作用和细胞质分布。碳点对细胞器的靶向作用有望用于癌症治疗；因此，研究了阳离子 CD 的细胞内转运和细胞毒性。基于我们之前的研究，我们使用季铵化碳点（QCDs）治疗和监测两种人类癌细胞 MCF-7 和 HeLa 系的行为。我们发现，在 QCDs 摄取方面，人类癌细胞和小鼠成纤维细胞之间存在相似性。QCDs 标记的 MCF-7 细胞的时程显微镜观察显示，细胞在最初的两个小时内死亡，低剂量比高剂量更快。浓度为 100 µg/mL 的 QCDs 在细胞死亡前进入细胞核；然而，在 200 µg/mL 的剂量下，细胞膜起泡，随后 QCDs 渗透到核区。在 HeLa 细胞的情况下，没有发生剂量依赖性效应；然而，标记的细胞也在有丝分裂中死亡，几乎在所有剂量下都发生了遗传毒性。此外，在用 100 µg/mL 的 QCDs 孵育 24 小时后，对比明显的细胞内隔室，可能是线粒体。根据浓度的不同，24 小时后活性氧（ROS）水平略有增加，因此遗传毒性可能是由纳米材料引起的。由于细胞周期的 G0/G1 期延长，DNA 损伤可能部分修复，因此细胞活力下降未达到 IC 50。因此，G2/M 期的缺陷可能允许受损细胞进入有丝分裂并经历细胞凋亡。两种细胞系的抗癌作用主要表现为遗传毒性。
