Molybdenum Disulfide Nanoparticles Resist Oxidative Stress-Mediated Impairment of Autophagic Flux and Mitigate Endothelial Cell Senescence and Angiogenic Dysfunctions

Abstract

The impairment of autophagy involves oxidative stress-induced cellular senescence, leading to endothelial dysfunctions and the onset of cardiovascular diseases. As molybdenum disulfide nanoparticles (MoS 2 NPs), representative transition metal dichacogenide materials, have great potential as a multifunctional therapeutic agent against various disorders, the present study aimed to investigate whether MoS 2 NPs prevents hydrogen peroxide (H 2 O 2 )induced endothelial senescence by modulating autophagic process. Our results showed that pretreatment with MoS 2 NPs inhibited H 2 O 2 -induced endothelial senescence and improved endothelial functions. Exposure of H 2 O 2 increased p62 level and blocked the fusion of autophagosomes with lysosomes, indicating of impaired autophagic flux in senescent endothelial cells. However, MoS 2 NPs pretreatment efficiently suppressed cellular senescence through triggering autophagy and resisting impaired autophagic flux. Furthermore, the genetic inhibition of autophagy by siRNA against Beclin 1 or ATG-5 directly abrogated the protective action of MoS 2 NPs on endothelial cells against H 2 O 2 -induced senescence.Thus, these results suggested that MoS 2 NPs rescue endothelial cells from H 2 O 2 -induced senescence by improving autophagic flux, and provide valuable information for the rational design of MoS 2 -based nanomaterials for therapeutic use in senescence-related diseases.

Nanocomposite of Poly(l-Lactic Acid) with Inorganic Nanotubes of WS2

“…Obviously, the nucleation of PLLA crystallites during the solvent evaporation was a prime factor in enhancing the mechanical properties of the polymer matrix. This study, together with the fact that these nanotubes are found to exhibit minor toxicity [34][35][36][37][38], opens up several opportunities to further explore these nanocomposites for different applications.…”

“…Furthermore, the addition of the nanotubes to different gels [32,33] and polymer matrices [34] in small amounts leads to a precipitous reduction in the friction forces, which may have important ramifications on numerous medical and other technologies. Equally important is the fact that several studies have indicated that IF/INT of WS 2 (MoS 2 ) are non-toxic and biocompatible [34][35][36][37][38]. One of the challenges in nanocomposites is the compatibility between the polymer matrix and the nanofillers, which entails that the interfacial interaction between the surfaces of the two phases cannot be easily tuned and matched.…”

Nano-Based Theranostic Tools for the Detection and Elimination of Senescent Cells

“…Several other strategies have been recently proposed to provide more accurate and targeted senolytic-based interventions. These include nanotechnology-based approaches for detection, site-specific delivery of senolytics and/or senoprobes, and successful elimination of SCs [ 83 , 107 , 108 , 109 , 110 ]. As cellular senescence may be implicated in the pathogenesis of age-related neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease [ 111 , 112 ], the use of nano-senolytics in the central nervous system (CNS) seems promising.…”

“…Functionalized nanomaterials appear to have a promising potential as nanocarriers and can be used for improving SC clearance. Table 1 provides published examples of in vitro and in vivo senotherapeutic action of nano-based drug delivery systems [ 83 , 107 , 108 , 109 , 110 , 114 , 118 , 119 , 120 , 121 ].…”

“…Targeted delivery of rapamycin (LR-CD9mAb) to diminish senescence of CD9-receptor-overexpressing cells was also explored and rapamycin was found to promote cell proliferation and reduce the levels of SA-β-gal-positive cells [ 118 ]. Another study performed by Ke et al [ 108 ] showed that MoS 2 NPs suppressed hydrogen-peroxide-induced senescence in endothelial cells. In addition, MoS 2 NP treatment leads to autophagy activation, which suppressed SIPS in vitro [ 108 ].…”