DNA-damage and cell cycle arrest initiated anti-cancer potency of super tiny carbon dots on MCF7 cell line

Abstract

While carbon-based materials have spearheaded numerous breakthroughs in biomedicine, they also have procreated many logical concerns on their overall toxicity. carbon dots (cDs) as a respectively new member have been extensively explored in nucleus directed delivery and bioimaging due to their intrinsic fluorescence properties coupled with their small size and surface properties. Although various in vitro/in vivo studies have shown that CDs are mostly biocompatible, sufficient information is lacking regarding genotoxicity of them and underlying mechanisms. This study aims to analyze the real-time cytotoxicity of super tiny CDs (2.05 ± 0.22 nm) on human breast cancer cells (MCF7) and human primary dermal fibroblast cell cultures (HDFa) by xCELLigence analysis system for further evaluating their genotoxicity and clastogenicity to evaluate the anti-tumor potential of cDs on breast adenocarcinoma. As combined with flow cytometry studies, comet assay and cytokinesisblock micronucleus assay suggest that the CDs can penetrate to the cell nuclei, interact with the genetic material, and explode DNA damage and G0/G1 phase arrest in cancer cells even at very low concentrations (0.025 ppm) which provide a strong foundation for the design of potentially promising cD-based functional nanomaterials for DnA-damage induced treatment in cancer therapy. Functional nanomaterials that can better target cancer cells that will improve prevention and therapy could be accomplished by the combined efforts of nanotoxicologists, cancer biologists and nanobiomaterial scientists focused on toxicology and related cancer therapy. Engineering carbon-based nanomaterials and their applications are among the most dynamic fields in modern advanced materials science and engineering 1-3. To date, various carbon nanomaterials such as carbon nanotubes 4,5 , fullerenes 6 , graphene 7,8 , graphene oxides 9 , carbon diamonds 10,11 , and carbon dots 12,13 have been synthesized and reported by various researchers. Among these, CDs have become particularly interesting because of their unique physical and chemical properties such as thermal and electrical conductivity, high mechanical strength together with their unique optic and fluorescence features 14-16. They have been used in bio-imaging, drug delivery, nucleus targeting, and labeling, photodynamic therapy, optoelectronics, solar cells, photocatalyst design, photodetectors, and many other biological and engineering fields 17-26. Several methods are available for the synthesis of CDs, namely, laser ablation 15 , electro-oxidation 27 or oxidative acid treatment 12 ; while nowadays, less laborsome and cheaper methods such as hydrothermal 28 and thermal synthesis 24,29,30 , microwave-assisted hydrothermal synthesis 31 , ultrasound synthesis 32 , etc. are popularly exercised. CDs can be synthesized either from inorganic materials 19,33 such as graphene 34 , carbon black 35 , and candle soot 12

A Strategic Review on Carbon Quantum Dots for Cancer-Diagnostics and Treatment

“…From TEM images show that DNA dots are spherical in shape and well separated from each other i.e., no aggregation is formed. In another work Simsek et al constructed CQDs from Nerium Oleander with an average size of 2.05 nm measured by TEM ( Şimşek et al, 2020 ). It is also revealed that CQDs possess a high crystalline structure with 0.21 nm spacing which corresponds to sp2 carbon.…”

“…CQDs enhance the intracellular concentration of drugs in cancer cells and keep away normal cells from toxicity. For example, Simsek et al synthesized carbon dots (CD) of size 2.05 nm from Nerium Oleander ( Şimşek et al, 2020 ). CQDs can penetrate cell nuclei to react with genes resulting in DNA damage, as explained in Figure 9 .…”

Pro-apoptotic property of phytocompounds from Naringi crenulata in HER2+ breast cancer cells in vitro

“…It imposes specific cellular dependencies upon cancer cells to sustain aberrant proliferation [42,43]. Şimşek et al [44] demonstrated that DNA-damage and cell cycle arrest initiated anticancer potency of super tiny carbon dots on MCF7 cell line, where the study identified cell cycle arrest in the G0/G1 phase and the induction of cell cycle arrest was reported to occur in a concentration-dependent manner. NCE compounds induce cell cycle arrest in SB RK3 cells, which is evaluated by cell cycle distribution by utilizing flow cytometry.…”

Polarity-dependent emission from hydroxyl-free carbon nanodots

“…Carbon nanodots (CNDs), which are the youngest members of the nanocarbon family being rich in graphene-based cores and carbonaceous surfaces, [1][2][3][4][5][6] possess several interesting properties including tunable emissions, 7,8 good chemical stabi-lity, 9 high photostability, 10 excellent biocompatibility 11 and photo-induced electron transfer ability. [12][13][14][15][16] The origin of photoluminescence (PL) in CNDs is usually attributed to their electronic bandgap, which can be modulated by several factors including size variations, structural defects, elemental doping, etc.…”