Abstract
Generally, platinum nanoparticles (PtNPs) are considered non-toxic; however, toxicity depends on the size, dose, and physico-chemical properties of materials. Owing to unique physico-chemical properties, PtNPs have emerged as a material of interest for several biomedical applications, particularly therapeutics. The adverse effect of PtNPs on the human monocytic cell line (THP-1) is not well-established and remains elusive. Exposure to PtNPs may trigger oxidative stress and eventually lead to inflammation. To further understand the toxicological properties of PtNPs, we studied the effect of biologically synthesized ultra-small PtNPs on cytotoxicity, genotoxicity, and proinflammatory responses in the human monocytic cell line (THP-1). Our observations clearly indicated that PtNPs induce cytotoxicity in a dose-dependent manner by reducing cell viability and proliferation. The cytotoxicity of THP-1 cells correlated with an increase in the leakage of lactate dehydrogenase, generation of reactive oxygen species, and production of malondialdehyde, nitric oxide, and carbonylated proteins. The involvement of mitochondria in cytotoxicity and genotoxicity was confirmed by loss of mitochondrial membrane potential, lower ATP level, and upregulation of proapoptotic and downregulation of antiapoptotic genes. Decreases in the levels of antioxidants such as reduced glutathione (GSH), oxidized glutathione (GSH: GSSG), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and thioredoxin (TRX) were indicative of oxidative stress. Apoptosis was confirmed with the significant upregulation of key apoptosis-regulating genes. Oxidative DNA damage was confirmed by the increase in the levels of 8-oxodG and 8-oxoG and upregulation of DNA damage and repair genes. Finally, the proinflammatory responses to PtNPs was determined by assessing the levels of multiple cytokines such as interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein 1 (MCP-1). All the cytokines were significantly upregulated in a dose-dependent manner. Collectively, these observations suggest that THP-1 cells were vulnerable to biologically synthesized ultra-small PtNPs.
Highlights
Owing to their catalytic and unique surface-related physicochemical properties, including high surface area, platinum nanoparticles (PtNPs) have garnered considerable interest in the automotive sector, chemical industry, and biomedical device manufacturing industry [1,2,3]
We investigated the cellular responses to PtNPs in THP-1 cells
The single sharp peak at 300 nm was attributed to the excitations of surface plasmon vibrations, indicating the synthesis of PtNPs (Figure 1A), which is in agreement with the results of previous reports [41,42]
Summary
Owing to their catalytic and unique surface-related physicochemical properties, including high surface area, platinum nanoparticles (PtNPs) have garnered considerable interest in the automotive sector, chemical industry, and biomedical device manufacturing industry [1,2,3]. Application of PtNPs in industry and biomedicine depends on several factors such as their size, shape and elemental composition, electronic surface structure, presence of capping agent, dispersion state, solubility, and cell type [3,7,8]. Several methods have been developed for PtNPs synthesis; these methods have several disadvantages, such as unnecessary toxic effects of nanoparticles due to the presence of various potential harmful contaminants or hazardous chemicals, production of high amounts of waste, and uncontrolled size. PtNPs are synthesized using bacteria [9], cyanobacteria [10,11], seaweeds [12], fungi [13], plants [14], and honey [15]
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