TFEB-lysosome pathway activation is associated with different cell death responses to carbon quantum dots in Kupffer cells and hepatocytes

Abstract

Background Carbon dot has been widely used in biomedical field as a kind of nanomaterial with low toxicity and high biocompatibility. CDs has demonstrated its unique advantages in assisted drug delivery, target diagnosis and targeted therapy with its small size and spontaneous fluorescence. However, the potential biosafety of CDs cannot be evaluated. Therefore, we focused on the study of liver, the target organ involved in CDs metabolism, to evaluate the risk of CDs in vitro. Methods and results Liver macrophage KUP5 cells and normal liver cells AML12 cells were incubated in CDs at the same concentration for 24 h to compare the different effects under the same exposure conditions. The study found that both liver cell models showed ATP metabolism disorder, membrane damage, autophagosome formation and lysosome damage, but the difference was that, KUP5 cells exhibited more serious damage than AML12 cells, suggesting that immunogenic cell type is particularly sensitive to CDs. The underlying mechanism of CDs-induced death of the two hepatocyte types were also assessed. In KUP5 cells, death was caused by inhibition of autophagic flux caused by autophagosome accumulation, this process that was reversed when autophagosome accumulation was prevented by 3-MA. AML12 cells had no such response, suggesting that the accumulation of autophagosomes caused by CDs may be specific to macrophages. Conclusion Activation of the TFEB-lysosome pathway is important in regulating autophagy and apoptosis. The dual regulation of ERK and mTOR phosphorylation upstream of TFEB influences the death outcome of AML12 cells. These findings provide a new understanding of how CDs impact different liver cells and contribute to a more complete toxicological safety evaluation of CDs.

Molecular mechanism of nanomaterials induced liver injury: A review

“…In in vitro study pretreatment of KUP5 cells with NAC ( N -acetylcysteine – ROS scavenger) and DHMEQ (Dehydroxymethylepoxyquinomicin- NF-KB translocation inhibitor) before QDs, reversed the activation of Kupffer cells following down-regulation of NF-κB, caspase-1, and NLRP3[ 174 ]. A recent study highlights the varied impact of CDs (Carbon Quantum Dots) on liver cells (KUP5 and AML12 cells in vitro ) and the importance of the TFEB-lysosome pathway in regulating autophagy and apoptosis induced by CDs on liver cells for a comprehensive toxicological safety evaluation[ 175 ]. Follow Table 17 for a comprehensive account.…”

Spatiotemporally Controllable Bifunctional Micellar-Carbon Dot Supernanoparticles for Wounds Healing

“…Carbon dots (CDs), an up-and-coming carbon-based nanomaterial, have garnered significant interest in the field of photosensitizers for photodynamic therapy due to their small size, strong dispersion, high solubility, excellent biocompatibility, good photostability, and outstanding light-induced charge transfer rate. ,,− Moreover, the easily modifiable structural characteristics render carbon dots more straightforward, efficient, and cost-effective in realizing multifunctional synergistic effects. , Doping CDs with metal ions is a potent tactic for modulating their physicochemical properties. ,− Cerium (Ce) is the most prevalent rare earth metal in the Earth’s crust. , Nanomaterials containing cerium exhibit reversible conversion properties between Ce 3+ (reduced state) and Ce 4+ (oxidized state) in a biological environment . This redox cycling renders them an effective scavenger for free radicals, as they donate or accept electrons to neutralize unstable radicals, thereby exerting excellent and enduring antioxidant effects. − Meanwhile, as semiconductor photocatalysts, Ce-based nanomaterials exhibit strong absorption in the ultraviolet region. , When incorporated into carbon-based materials, Ce markedly enhances the suppression of electron–hole recombination and interaction with charge carriers, thereby significantly enhancing their ROS photocatalytic generation capability. ,− Ce-doped CDs are recognized as optimal nanomaterials with substantial application value for promoting wound healing.…”