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Nanotoxicology and Regulatory Aspects of Nanomaterials and Nanomedicines
Published in Yasser Shahzad, Syed A.A. Rizvi, Abid Mehmood Yousaf, Talib Hussain, Drug Delivery Using Nanomaterials, 2022
Clathrin-dependent endocytosis is the most characterized endocytosis process as far it's the most active and constitutively present in all types of cells (Wang et al., 2020). Its role is essential for the cellular hemostasis for nutrients and macromolecule transport such as cholesterol via low density lipoproteins (LDL receptors), and iron via transferrin (Tfn receptors) that are considered as markers for this route of uptake, serum proteins, membranous ion pumps. It has a crucial role in cellular communication during organogenesis, cell signalling regulation by controlling and downregulation of receptor levels, synaptic neuronal transmission (Ca+2-gated channels regulation, recycling of neurotransmitter vesicles), and reabsorption of serum proteins after filtration in kidney tubules (Kaksonen and Roux, 2018; López-Hernández et al., 2020). It is membranous invaginations mediated through clathrin triskelia that coat or cage the incoming vesicles (Conner and Schmid, 2003). It is initiated by a binding of certain ligands to surface receptors at clathrin-nucleation sites/pits with subsequent clathrin-1 protein assembly with the adaptor/assembly protein complexes into clathrin-coated lattices. Dynamin GTPase scission mechanism proceeds around the vesicle neck. Clathrisome disassemble its coatings prior to fusion with the endolysosmes. The molecules/particles size ranges from ~100 to 200 nm (Wang et al., 2020).
Uptake of Gold Nanoparticles into Mammalian Cells
Published in Lev Dykman, Nikolai Khlebtsov, Gold Nanoparticles in Biomedical Applications, 2017
In a subsequent report from the same group [194], the study of uptake of gold NRs into various types of cells was continued by using A549 carcinoma cells, 16HBE normal bronchial epithelial cells, and mesenchymal stem cells. The intracellular uptake of 55 × 13-nm NRs functionalized with fetal bovine serum was examined by ICP–MS and TEM. It was found that uptake was more effective in the carcinoma and stem cells and was much worse in the normal cells. Exocytosis was more active in the stem cells. To investigate the mechanism of endocytosis, the authors used a variety of inhibitors. Sodium azide, 2-deoxy-d-glucose, and low temperature sharply decreased the endocytosis (to as low as 80%) and noticeably decreased ATP synthesis—that is, the endocytosis was energy demanding. The use of chlorpromazine and a hypertonic solution of sucrose as inhibitors reduced NR uptake by 75 and 89%, respectively. It follows that the principal mechanism of endocytosis was clathrin dependent. If nystatin, methyl-β-cyclodextrin, and dynamin were served as inhibitors, the endocytosis decreased by 54%, 48%, and 42%, respectively, attesting that a raft-dependent endocytosis route is also possible. TEM data indicated that the intracellular localization of NRs was different in the three types of cells: only in the carcinoma cells were NRs present in mitochondria as well as in lysosomes. The authors associated the toxic effect of NRs on the cancer cells with mitochondrial damage by CTAB, which is released in the lysosomes of cancerous cells. Thus, cell viability is affected not only by endocytosis routes but also (and primarily) by intracellular localization.
Effects of Nanocrystal Morphologies on Cytotoxicity
Published in Suresh C. Pillai, Yvonne Lang, Toxicity of Nanomaterials, 2019
The effect of shape on the cellular uptake of gold NPs has also been investigated by Xie et al. (2017). Three different types of methylpolyethylene glycol-coated gold NPs were prepared: stars, rods, and triangles. The uptake of these particles by RAW 264.7 cells was then analysed. Interestingly, it was found that the different particle shapes employed different mechanisms for cell entry. The star-shaped particles entered the cells via clathrin-mediated uptake, whereas the gold nanorods employed this mechanism but also took advantage of caveolae/lipid raft-mediated endocytosis. The gold nanotriangles entered the cells via multiple routes including clathrin-mediated endocytosis and a dynamin-dependent pathway.
Toxicity in vitro reveals potential impacts of microplastics and nanoplastics on human health: A review
Published in Critical Reviews in Environmental Science and Technology, 2022
Qingying Shi, Jingchun Tang, Rutao Liu, Lan Wang
In biological fluids, proteins bind to the surface of nanoparticles to form a coating known as the protein corona, which can critically affect the interaction of the nanoparticles with cells (Jiang et al., 2010b). It’s reported that in the presence or absence of serum, the uptake mechanisms were distinguished from all tested cell types and functionalized PS NPs particles (Lunov et al., 2011a). Macrophages internalized the carboxylated PS particles mainly via clathrin-dependent and dynamin-dependent endocytosis and the amino-functionalized PS particles were apparently taken up via macropinocytosis in buffer, whereas macrophages apparently internalized both carboxylated and amino-functionalized NPs mainly by phagocytosis in serum-containing medium. Also, THP-1 cells took up both carboxylated PS particles and amino-functionalized PS particles by macropinocytosis under buffer conditions, while they apparently took up both NPs by dynamin-dependent endocytosis in the presence of serum.
Epigenetic modifications associated with pathophysiological effects of lead exposure
Published in Journal of Environmental Science and Health, Part C, 2019
Madiha Khalid, Mohammad Abdollahi
Apoptosis is triggered via the cascading action of several enzymes under the control of complex signaling pathways. Closely related apoptotic genes belong to Bcl-2 families such as Bax and Bad genes, i.e., Bcl-2 is an associated agonist of cell death, while Bcl-2/w/xl, the apoptosis regulator Mcl-1, and the anti-apoptotic protein NR-13 oppose apoptosis.275,276 Pb triggers apoptosis via inducing oxidative stress. It induces oxidative stress by decreasing the mRNA expression level of glycometabolism enzymes,277,278 MDA-mediated lipid peroxidation,279,280 and by decreasing SOD and GSH-Px activity.281,282 Oxidative stress leads to mitochondrial dysfunction which ultimately triggers apoptosis,283 characterized by abnormal activity of Bax, p53, mitochondrial cytochrome-c (Cyt-c), caspase-3 and caspase-981,284 (Figure 5). Studies with chicken liver demonstrated an increased number of apoptotic cells (P < 0.05) as a result of 350 mg/L Pb exposure. Reduced levels of metabolic enzymes were observed, including Na+-K+-ATPase, Ca2+-ATPase, Mg2+-ATPase, and ROS scavenging enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) (P < 0.05). The levels of iNOS, MDA, and NO (P < 0.05) were significantly increased, suggesting Pb-induced imbalance among metabolic and ROS scavenging enzymes. Decreased mRNA levels for hexokinase (HK2), sarcosine dehydrogenase (SDH), plucked (PK), and pyruvate dehydrogenase complex component X (PDHX) were observed (P < 0.05). Pb exposure caused decreased mRNA expression levels of mitochondrial fission and fusion genes and their corresponding proteins (P < 0.05) such as fission-mitochondrial 1 (Fis1), dynamin-related protein 1 (Drp1), OPA1 mitochondrial dynamin-like GTPase (OPA1), and mitofusin 1/2 (Mfn1/2). The mRNA levels of some apoptotic genes and their corresponding proteins levels were increased, such as p53, Cyt-c, Bax, caspase-3, and caspase-9 (P < 0.05) except Bcl-2, suggesting Pb-induced apoptosis due to imbalance of different pro-apoptotic and anti-apoptotic factors as displayed by ruptured cells, swelling, chromosome condensation, cell body shrinkage, and mitochondrial vacuolization in the liver.285 Similarly, many studies reported Pb-induced cytoplasmic swelling, nuclear vesiculation, hepatic cellular damage, necrosis, and histopathological alterations in the liver.286–288