Flower-Like Molybdenum Disulfide Nanostructures for Promoting Mitochondrial Homeostasis and Attenuating Inflammatory Endothelial Dysfunction

Abstract

Mitochondrial dynamics is crucial to cellular metabolic homeostasis, development, and remodeling. However, the perturbation of mitochondrial dynamics impairs endothelial functions, leading to numerous diseases, including cardiovascular diseases. The few-layered molybdenum disulfide (MoS 2 )-based nanoagents hold great potential as therapeutic agents for various disorders. Herein, we investigated whether flower-like MoS 2 nanosheets (FL-MoS 2 ) promote mitochondrial homeostasis via modulating mitochondrial dynamics in endothelial cells. Our results demonstrated that mitochondrial elements become dramatically elongated in endothelial cells in response to FL-MoS 2 , suggesting that FL-MoS 2 promotes mitochondrial fusion rather than fission. The molecular mechanisms mediating mitochondrial fusion by FL-MoS 2 involved the upregulation of pro-fusion proteins as well as a decrease in mitochondrial translocation of dynamin-related protein 1 (Drp1). Consistently, we demonstrated that FL-MoS 2 maintains mitochondrial homeostasis through regulating transcription factor EB (TFEB)-mediated mitochondrial dynamics and biogenesis. In addition, we established that mitochondrial tubulation in response to FL-MoS 2 protects endothelial cells from mitochondrial impairments induced by tumor necrosis factor (TNF) α. Our results revealed the unique ability of MoS 2 -based nanoagents to modulate mitochondrial homeostasis, contributing to improvements in endothelial functions.

Modified TPP-MoS2 QD Blend as a Bio-Functional Model for Normalizing Microglial Dysfunction in Alzheimer’s Disease

“…Abundant studies have demonstrated the anti-inflammatory action of MoS 2 nanoparticles on different cells [ 39 , 40 ], and the results of that study support our findings. The mechanisms of action by which the DSPE-PEG-TPP/MoS 2 QD blend was able to produce neuroprotective effects and reduce inflammation were not mentioned; however, many studies using natural products and pharmacological drugs have reported that a protective effect against Aβ oligomers-induced microglial activation and inflammation cascades is achieved via suppression of the master switch for microglial activation, i.e., the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), which plays a crucial regulatory function in the generation of inflammatory mediators resulting in neurotoxicity.…”

“…One previous study found that flower-like MoS2 nanosheets (FL-MoS2) caused endothelial cells to shift toward mitochondrial fusion rather than fission, as demonstrated by increased expression of mitochondrial fusion proteins (Mfn2, Opa1) and decreased expression of fission proteins (Fis1) which promote mitochondrial homeostasis [39]. Lastly, the anti-inflammatory impact of the DSPE-PEG-TPP/MoS2 QD blend on microglial cells activated by Aβ was determined using the ELISA technique and real-time PCR analysis.…”

“…As can be seen from the data, the DSPE-PEG-TPP/MoS2 blend regulates microglial activation by reducing the cytokine level of inflammatory markers and increasing the level of cytoprotective markers (Figure 6). One previous study found that flower-like MoS 2 nanosheets (FL-MoS 2 ) caused endothelial cells to shift toward mitochondrial fusion rather than fission, as demonstrated by increased expression of mitochondrial fusion proteins (Mfn2, Opa1) and decreased expression of fission proteins (Fis1) which promote mitochondrial homeostasis [39].…”

“…One previous study found that flower-like MoS 2 nanosheets (FL-MoS 2 ) caused endothelial cells to shift toward mitochondrial fusion rather than fission, as demonstrated by increased expression of mitochondrial fusion proteins (Mfn2, Opa1) and decreased expression of fission proteins (Fis1) which promote mitochondrial homeostasis [ 39 ].…”