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Self-Assembled Organic Nanotubes: Novel Bionanomaterials for Orthopedics and Tissue Engineering
Published in Tuan Vo-Dinh, Nanotechnology in Biology and Medicine, 2017
Rachel L. Beingessner, Baljit Singh, Thomas J. Webster, Hicham Fenniri
Because the ultimate goal for a drug delivery system is to target certain cells to maximize the therapeutic activity and minimize adverse effects, we have also explored and demonstrated that the RNT surface functional groups can be used to target particular cell receptors. The αvβ3 integrin on human adenocarcinoma cells (Calu-3), for example, recognizes the arginine-glycine-aspartic acid (RGD) peptide sequence.142 By treating these Calu-3 cells with coassembled RNTs-K1/RGDSK, cell inflammation and apoptosis can be triggered through the P38 MAPK pathway (Figure 2.9).142 This is significant because the αvβ3 integrin is generally not expressed in normal and resting endothelial cells but is present in proliferating endothelial cells in tumors. The importance of the RNT functional groups in initiating this cellular response is apparent by comparing with RNTs-K1, which, in contrast, are biocompatible and do not promote a robust inflammatory response or cytotoxicity in the same Calu-3 cells168 as well as in U937 human macrophage cells169 and upon pulmonary exposure of C57/BL mice in vivo.170
Static, Low-Frequency, and Pulsed Magnetic Fields in Biological Systems
Published in James C. Lin, Electromagnetic Fields in Biological Systems, 2016
Dini et al. (2009) investigated the morphofunctional influence of an SMF (6 mT, for 72 hours) during differentiation induced by 12-O-tetradecanoyl-13-phorbol acetate (TPA, 50 ng/ml) in human leukaemia U937 cells. The cell morphology of U937 cells was investigated by optic and electron microscopy. Specific antibodies or molecules or both were used to label CD11c, CD14, phosphatidylserine, and F-actin and to investigate the distribution and activity of lysosomes, mitochondria, and smooth endoplasmic reticulum (SER). The ion [Ca2+]i was evaluated with a spectrophotometer. The degree of differentiation in SMF-exposed cells was lower than that of nonexposed cells in a time-dependent manner. The SMF-exposed cells showed cell shape and F-actin modification, inhibition of cell attachment, appearance of membrane roughness and large blebs, and impaired expression of specific macrophagic markers on the cell surface. The intracellular localization of SER and lysosomes was only partially affected by exposure. A significant localization of mitochondria with an intact membrane potential at the cell periphery in nonexposed, TPA-stimulated cells was observed; conversely, in the presence of SMF mitochondria were mainly localized near the nucleus. In no case did SMF exposure affect cell viability. The authors suggested that the sharp intracellular increase of [Ca2+]i could be one of the causes of the aforementioned changes.
Cobalt Toxicity and Human Health
Published in Debasis Bagchi, Manashi Bagchi, Metal Toxicology Handbook, 2020
Md. Hafiz Uddin, Marufa Rumman
Tungsten carbide (WC) shows less toxicity to the cells; however, when attached with Co-NPs (WC-Co-NPs) its toxicity is enhanced almost similar to cobalt ions (Co2+) in human keratinocytes (HaCaT). Gene expression analysis showed that WC exerted very little effects on the transcriptomic level after 3 and 72 h of exposure, whereas WC-Co-NPs caused significant transcriptional changes that were similar to Co2+. Gene set enrichment analyses revealed that the differentially expressed genes were related to hypoxia response, carbohydrate metabolism, endocrine pathways, cell adhesion, and targets of several transcription factors (e.g., SOX2, YY1) [10]. Cobalt ferrite nanoparticles (Co-Fe-NPs) have great advantages compared to other contestants because of its physicochemical and magnetic properties with ease of synthesis resulting in extensive use in biomedical fields. Human body can be exposed to Co-Fe-NPs easily by ingestion, inhalation, adsorption, etc. which might induce oxidative stress, cytotoxicity, genotoxicity, inflammation, apoptosis, and developmental, metabolic, and hormonal abnormalities [37]. Research has shown the putative role of the hypoxia-inducible factor (HIF) pathway in the mechanism of Co-NPs toxicity (Figure 15.1) in human macrophage models using the U937 cell line, human alveolar macrophages, and monocyte-derived macrophages. Co-NPs induced HIF-1α stabilization which can be prevented by the addition of either ascorbic acid (100 mM) or glutathione (1 mM) suggesting the involvement of ROS-independent pathway in Co-NPs-induced cytotoxicity. Additionally, ascorbic acid causes the downregulation of IL-1b showing a possible link between HIF and the inflammatory response to Co-NPs [19].
Proteolytically degradable PEG hydrogel matrix mimicking tumor immune microenvironment for 3D co-culture of lung adenocarcinoma cells and macrophages
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Human myeloid leukemia U937 cells were used as a model monocyte. U937 cells were maintained in RPMI-1640 containing 10% fetal bovine serum and 1% antibiotic-antimycotic at 37 °C and 5% CO2. Culture medium was replaced every 2–3 days. For differentiation into M0 macrophages, cells were suspended on tissue culture plates at a density of 5,700 cell/cm2 and treated with 100 ng/mL phorbol 12-myristate 13-acetate (PMA) for 48 h. Then, the medium containing PMA was replaced with normal medium and cells were cultured for another 24 h. For M1 type polarization, M0 macrophages were treated with 100 ng/mL lipopolysaccharide (LPS) for 24 h.