PMID- 35162996 OWN - NLM STAT- MEDLINE DCOM- 20220307 LR - 20220307 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 3 DP - 2022 Jan 19 TI - Intracellular Trafficking of Cationic Carbon Dots in Cancer Cell Lines MCF-7 and HeLa-Time Lapse Microscopy, Concentration-Dependent Uptake, Viability, DNA Damage, and Cell Cycle Profile. LID - 10.3390/ijms23031077 [doi] LID - 1077 AB - 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 microg/mL entered into the nucleus before cellular death; however, at a dose of 200 microg/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 microg/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. FAU - Havrdova, Marketa AU - Havrdova M AD - Regional Centre of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute (CATRIN), Palacky University Olomouc, Krizkovskeho 511/8, 779 00 Olomouc, Czech Republic. FAU - Urbancic, Iztok AU - Urbancic I AUID- ORCID: 0000-0003-3603-6585 AD - Laboratory of Biophysics, Condensed Matter Physics Department, Jozef Stefan Institute, Jamova Cesta 39, 1000 Ljubljana, Slovenia. FAU - Tomankova, Katerina Barton AU - Tomankova KB AUID- ORCID: 0000-0002-3249-4522 AD - Department of Medical Biophysics, Faculty of Medicine and Dentistry, Institute of Translational Medicine, Palacky University in Olomouc, Hnevotinska 3, 775 15 Olomouc, Czech Republic. FAU - Malina, Lukas AU - Malina L AD - Department of Medical Biophysics, Faculty of Medicine and Dentistry, Institute of Translational Medicine, Palacky University in Olomouc, Hnevotinska 3, 775 15 Olomouc, Czech Republic. FAU - Polakova, Katerina AU - Polakova K AUID- ORCID: 0000-0003-2994-4075 AD - Regional Centre of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute (CATRIN), Palacky University Olomouc, Krizkovskeho 511/8, 779 00 Olomouc, Czech Republic. FAU - Strancar, Janez AU - Strancar J AD - Laboratory of Biophysics, Condensed Matter Physics Department, Jozef Stefan Institute, Jamova Cesta 39, 1000 Ljubljana, Slovenia. FAU - Bourlinos, Athanasios B AU - Bourlinos AB AD - Physics Department, University of Ioannina, 45110 Ioannina, Greece. LA - eng GR - CZ.02.1.01/0.0/0.0/16_019/0000754/Nano4Future/ GR - CZ.02.1.01/0.0/0.0/17_048/0007323/Development of pre-applied research in nanotechnogy and biotechnology/ GR - NU21-09-00357/The Ministry of Health of the Czech Republic - MZCR/ GR - CZ. 02. 1. 01/0.0/0.0/16_019/0000868/The work was supported also by the European Regional Development Fund - Project ENOCH/ GR - P1-0060/Slovenian Research Agency for funding/ PT - Journal Article DEP - 20220119 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Reactive Oxygen Species) RN - 7440-44-0 (Carbon) SB - IM MH - Animals MH - Biological Transport MH - Carbon/chemistry/*pharmacokinetics/pharmacology MH - Cell Line MH - Cell Proliferation MH - Cell Survival/drug effects MH - DNA Damage MH - Fibroblasts/*cytology/drug effects/metabolism MH - G2 Phase Cell Cycle Checkpoints/drug effects MH - HeLa Cells MH - Humans MH - MCF-7 Cells MH - Mice MH - Neoplasms/drug therapy/genetics/*metabolism MH - Optical Imaging MH - Quantum Dots/*chemistry MH - Reactive Oxygen Species/*metabolism MH - Time-Lapse Imaging/*methods PMC - PMC8835431 OTO - NOTNLM OT - HeLa OT - MCF-7 OT - cancer cells OT - cationic carbon dots OT - cytotoxicity OT - fluorescence microspectroscopy OT - genotoxicity OT - nucleus COIS- The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2022/02/16 06:00 MHDA- 2022/03/08 06:00 PMCR- 2022/01/19 CRDT- 2022/02/15 01:16 PHST- 2021/12/06 00:00 [received] PHST- 2022/01/07 00:00 [revised] PHST- 2022/01/14 00:00 [accepted] PHST- 2022/02/15 01:16 [entrez] PHST- 2022/02/16 06:00 [pubmed] PHST- 2022/03/08 06:00 [medline] PHST- 2022/01/19 00:00 [pmc-release] AID - ijms23031077 [pii] AID - ijms-23-01077 [pii] AID - 10.3390/ijms23031077 [doi] PST - epublish SO - Int J Mol Sci. 2022 Jan 19;23(3):1077. doi: 10.3390/ijms23031077.