The role of nanoparticle size in hemocompatibility.
ABSTRACT It is expected that nanoparticular matters will be increasingly used for industrial and medical applications. Since it is known that nanoparticles exhibit unique and potential hazardous properties due to their small size, toxicity studies, risk assessment and risk management are of great interest. We focussed on adverse effects on human blood. Processes which warrant special attention are clotting, reactions triggering inflammatory and immune responses and hemolysis. Starting with the determination of size and surface charge in different media we assessed the effect of size and surface charge on induction of coagulation, thrombocyte activation, complement activation, granulocyte activation and hemolysis. We used polystyrene particles as model because they are available in different sizes but constant surface charges. The presence of salts and of protein in the dispersion solution increased particle size and neutralized surface charge. Positively charged particles formed aggregates in buffered solution. Interference of the particles with assays based on fluorescence associated cell sorting was identified. Positive surface charge induced activation of complement. Small size caused thrombocyte and granulocyte activation, and hemolysis. A characterization of particle size and surface charge in the solutions used for the experiments appears important for interpretation of the results. The size dependency of adverse effects in human blood is not linear; negatively charged particles larger than 60 nm hydrodynamic diameter appear to be considerably less hematotoxic than smaller ones.
Article: Role of surface charge and oxidative stress in cytotoxicity of organic monolayer-coated silicon nanoparticles towards macrophage NR8383 cells.[show abstract] [hide abstract]
ABSTRACT: Surface charge and oxidative stress are often hypothesized to be important factors in cytotoxicity of nanoparticles. However, the role of these factors is not well understood. Hence, the aim of this study was to systematically investigate the role of surface charge, oxidative stress and possible involvement of mitochondria in the production of intracellular reactive oxygen species (ROS) upon exposure of rat macrophage NR8383 cells to silicon nanoparticles. For this aim highly monodisperse (size 1.6 ± 0.2 nm) and well-characterized Si core nanoparticles (Si NP) were used with a surface charge that depends on the specific covalently bound organic monolayers: positively charged Si NP-NH2, neutral Si NP-N3 and negatively charged Si NP-COOH. Positively charged Si NP-NH2 proved to be more cytotoxic in terms of reducing mitochondrial metabolic activity and effects on phagocytosis than neutral Si NP-N3, while negatively charged Si NP-COOH showed very little or no cytotoxicity. Si NP-NH2 produced the highest level of intracellular ROS, followed by Si NP-N3 and Si NP-COOH; the latter did not induce any intracellular ROS production. A similar trend in ROS production was observed in incubations with an isolated mitochondrial fraction from rat liver tissue in the presence of Si NP. Finally, vitamin E and vitamin C induced protection against the cytotoxicity of the Si NP-NH2 and Si NP-N3, corroborating the role of oxidative stress in the mechanism underlying the cytotoxicity of these Si NP. Surface charge of Si-core nanoparticles plays an important role in determining their cytotoxicity. Production of intracellular ROS, with probable involvement of mitochondria, is an important mechanism for this cytotoxicity.Particle and Fibre Toxicology 01/2010; 7:25. · 7.25 Impact Factor
Article: Effect of surface properties of silica nanoparticles on their cytotoxicity and cellular distribution in murine macrophages.[show abstract] [hide abstract]
ABSTRACT: Surface properties are often hypothesized to be important factors in the development of safer forms of nanomaterials (NMs). However, the results obtained from studying the cellular responses to NMs are often contradictory. Hence, the aim of this study was to investigate the relationship between the surface properties of silica nanoparticles and their cytotoxicity against a murine macrophage cell line (RAW264.7). The surface of the silica nanoparticles was either unmodified (nSP70) or modified with amine (nSP70-N) or carboxyl groups (nSP70-C). First, the properties of the silica nanoparticles were characterized. RAW264.7 cells were then exposed to nSP70, nSP70-N, or nSP70-C, and any cytotoxic effects were monitored by analyzing DNA synthesis. The results of this study show that nSP70-N and nSP70-C have a smaller effect on DNA synthesis activity by comparison to unmodified nSP70. Analysis of the intracellular localization of the silica nanoparticles revealed that nSP70 had penetrated into the nucleus, whereas nSP70-N and nSP70-C showed no nuclear localization. These results suggest that intracellular localization is a critical factor underlying the cytotoxicity of these silica nanoparticles. Thus, the surface properties of silica nanoparticles play an important role in determining their safety. Our results suggest that optimization of the surface characteristics of silica nanoparticles will contribute to the development of safer forms of NMs.Nanoscale Research Letters 01/2011; 6(1):93. · 2.73 Impact Factor