Abstract
Silver nanoparticles (AgNPs) are one of the most investigated metal-based nanomaterials. Their biocidal activity boosted their application in both diagnostic and therapeutic medical systems. It is therefore crucial to provide sound evidences for human-related safety of AgNPs. This study aimed to enhance scientific knowledge with regard to biomedical safety of AgNPs by investigating how their different surface properties affect human immune system. Methods: preparation, characterization and stability evaluation was performed for four differently coated AgNPs encompassing neutral, positive and negative agents used for their surface stabilization. Safety aspects were evaluated by testing interaction of AgNPs with fresh human peripheral blood mononuclear cells (hPBMC) by means of particle cellular uptake and their ability to trigger cell death, apoptosis and DNA damages through induction of oxidative stress and damages of mitochondrial membrane. Results: all tested AgNPs altered morphology of freshly isolated hPBMC inducing apoptosis and cell death in a dose- and time-dependent manner. Highest toxicity was observed for positively-charged and protein-coated AgNPs. Cellular uptake of AgNPs was also dose-dependently increased and highest for positively charged AgNPs. Intracellularly, AgNPs induced production of reactive oxygen species (ROS) and damaged mitochondrial membrane. Depending on the dose, all AgNPs exhibited genotoxic potential. Conclusions: this study provides systematic and comprehensive data showing how differently functionalized AgNPs may affect the human immune system. Presented results are a valuable scientific contribution to safety assessment of nanosilver-based blood-contacting medical products.
Highlights
In today’s nano-world, two ‘ologies’ are constantly opposed: nanotechnology and nanotoxicology—one is trying to convince public about the usefulness of nanomaterials (NMs), while the other is trying to warn about potential nano-hazard on human health
For the treatment of human peripheral blood mononuclear cells (hPBMC), well characterized AgNPs were used that were freshly synthesized before cell experiments
Characterization and stability evaluation performed by DLS, electrophoretic light scattering (ELS), TEM and GFAAS (Figure 1 and Table 1) confirmed that AgNPs were of desired colloidal stability and properties, i.e., spherical in shape and 10 nm sized
Summary
In today’s nano-world, two ‘ologies’ are constantly opposed: nanotechnology and nanotoxicology—one is trying to convince public about the usefulness of nanomaterials (NMs), while the other is trying to warn about potential nano-hazard on human health. In the case of AgNPs, strong oxidative activity and release of very toxic Ag ions may lead to oxidative stress induction in human cells and tissues through production of reactive oxygen species (ROS) and depletion of mitochondrial membrane potential (∆ψm), representing initial proapoptotic signal [10,11]. Consequences of such oxidative stress may be numerous such as cytotoxicity, programmed cell death, genotoxicity, activation or supression of immune system [12,13,14].
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