Nanotoxicity of Silver Nanoparticles to Red Blood Cells: Size Dependent Adsorption, Uptake, and Hemolytic Activity

Abstract

Silver nanoparticles (AgNPs) are increasingly being used as antimicrobial agents and drug carriers in biomedical fields. However, toxicological information on their effects on red blood cells (RBCs) and the mechanisms involved remain sparse. In this article, we examined the size dependent nanotoxicity of AgNPs using three different characteristic sizes of 15 nm (AgNPs15), 50 nm (AgNPs50), and 100 nm (AgNPs100) against fish RBCs. Optical microscopy and transmission electron microscopy observations showed that AgNPs exhibited a size effect on their adsorption and uptake by RBCs. The middle sized AgNPs50, compared with the smaller or bigger ones, showed the highest level of adsorption and uptake by the RBCs, suggesting an optimal size of ∼50 nm for passive uptake by RBCs. The toxic effects determined based on the hemolysis, membrane injury, lipid peroxidation, and antioxidant enzyme production were fairly size and dose dependent. In particular, the smallest sized AgNPs15 displayed a greater ability to induce hemolysis and membrane damage than AgNPs50 and AgNPs100. Such cytotoxicity induced by AgNPs should be attributed to the direct interaction of the nanoparticle with the RBCs, resulting in the production of oxidative stress, membrane injury, and subsequently hemolysis. Overall, the results suggest that particle size is a critical factor influencing the interaction between AgNPs and the RBCs.

The in Vitro Effect of Polyvinylpyrrolidone and Citrate Coated Silver Nanoparticles on Erythrocytic Oxidative Damage and Eryptosis

“…We incubated the erythrocytes with vehicle or PVPor CT-AgNPs for 4 h; a time point similar to previous in vitro studies [18,31]. The various concentrations of PVP-and CT-AgNPs (2.5, 10 and 40 µg/ml) used in our study are also similar to previous studies evaluating nanotoxicity and blood compatibility of erythrocytes incubated with AgNPs [17,23]. Our concentrations are comparable with previous studies using AgNPs on human, mouse and fish erythrocytes and the highest dose of 40 µg/ml, is much lower than the optimal dose of AgNPs (200 µg/ml) that has been reported to induce hemolysis in human erythrocytes [17,18,23,[32][33][34].…”

“…In addition, studies using human erythrocytes have investigated the effects of AgNPs on hemolysis, morphology and their uptake [17,18]. Nevertheless, the mechanism underlying the pathophysiological effects of AgNPs on erythrocytes physiology is not fully understood.…”

Antibacterial properties and toxicity from metallic nanomaterials

“…53 Cytotoxicity of AgNPs on red blood cells (RBCs) is of particular interest, as the introduction of AgNPs into the body suggests a high probability of these into the blood. Chen et al 54 found cytotoxicity effects of 15, 50, and 100 nm AgNPs on RBC to be higher when they are a smaller size, while biological-based nanoparticles with larger sizes exhibit higher cytotoxic effects. This points to a possible difference in toxicity mechanism from one type of nanoparticle to the next.…”

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

“…42 (Asp) 8 -PEG-PCL nanoparticles designed in this study had the hydrophilic surface of PEG and the hydrophilic The effect of nanoparticles on erythrocyte aggregation indicates hemocompatibility of the nanoparticles. 43 Copolymer containing PEG-PCL has been reported to be hemocompatible and biocompatible. 44,45 In this study, we found that (Asp) 8 -PEG-PCL nanoparticles were hemocompatible, and biocompatible to osteoblasts and endothelial cells.…”