Toxic effects and involved molecular pathways of nanoparticles on cells and subcellular organelles

Abstract

Owing to the increasing application of engineered nanoparticles (NPs), besides the workplace, human beings are also exposed to NPs from nanoproducts through the skin, respiratory tract, digestive tract and vein injection. This review states pathways of cellular uptake, subcellular distribution and excretion of NPs. The uptake pathways commonly include phagocytosis, micropinocytosis, clathrin‐ and caveolae‐mediated endocytosis, scavenger receptor‐related pathway, clathrin‐ or caveolae‐independent pathway, and direct penetration or insertion. Then the ability of NPs to decrease cell viability and metabolic activity, change cell morphology, and destroy cell membrane, cytoskeleton and cell function was presented. In addition, the lowest dose decreasing cell metabolic viability compared with the control or IC50 of silver, titanium dioxide, zinc oxide, carbon black, carbon nanotubes, silica, silicon NPs and cadmium telluride quantum dots to some cell lines was gathered. Next, this review attempts to increase our understanding of NP‐caused adverse effects on organelles, which have implications in mitochondrial dysfunction, endoplasmic reticulum stress and lysosomal rupture. In particular, the disturbance of mitochondrial biogenesis and mitochondrial dynamic fusion‐fission, mitophagy and cytochrome c‐dependent apoptosis are involved. In addition, prolonged endoplasmic reticulum stress will result in apoptosis. Rupture of the lysosomal membrane was associated with inflammation, and both induction of autophagy and blockade of autophagic flow can result in cytotoxicity. Finally, the network mechanism of the combined action of multiple organelle dysfunction, apoptosis, autophagy and oxidative stress was discussed.

Silica nanoparticles induce lung inflammation in mice via ROS/PARP/TRPM2 signaling-mediated lysosome impairment and autophagy dysfunction

“…Besides, lysosome impairment and autophagy dysfunction are attracting growing attention for SiNPs-induced damages [8,9]. Lysosomes contain diverse acidic hydrolases, such as cathepsins, and nanoparticles are reported to accumulate in the lysosomes by endocytosis and subsequently induce cathepsin-dependent inflammation [10]. Recent studies suggest that NPs induce activation of the NLRP3 inflammasome and generation of interleukin-1β (IL-1β) via lysosomal rupture and consequent release of cathepsins [11,12].…”

<p>Multi-Walled Carbon Nanotubes (MWCNTs) Activate Apoptotic Pathway Through ER Stress: Does Surface Chemistry Matter?</p>

“…It has been previously shown that NM exposure could induce ER stress of cells, which consequently leads to the activation of apoptosis pathway 19. Meanwhile, NM-induced oxidative stress might also lead to prolonged ER stress 19,20. For MWCNTs, we recently showed that MWCNTs could activate ER stress in HUVECs, which is related with the lengths12 and diameters13 of MWCNTs.…”

Cellular Responses of Human Lymphatic Endothelial Cells to Carbon Nanomaterials

“…Considering that suppression of cell growth influences the increase in uptake rate of MWCNT, the uptake rate of CNHs is actually highest. We have reported that intracellular uptake of MWCNT in non-phagocytic cell lines may be due to three types of endocytosis as well as uptake by alternative pathways [50], and Liu et al, recently published a review of intracellular uptake of nanoparticles [51]. However, the molecular mechanism by which cells first recognize nanomaterials remains unclear.…”