Not all silver nanoparticles are equal: Effect of functionalization on K homeostasis in human red blood cells

Abstract

Although silver nanoparticles (AgNPs) are one of the most frequently used nanomaterials (NMs) in industrial and biomedical applications, their toxicity and interaction with blood components, such as erythrocytes, has been insufficiently investigated. Here, we report on the effect of AgNPs at the level of cellular function, and particularly on ion transport in human red blood cells (HRBCs). These AgNPs were size‐selected, concentrated and purified by tangential flow filtration before HRBC exposure. Two methods of synthesis were used for the functionalization of AgNPs, Creighton and Lee‐Meisel. HRBCs were obtained from adult donors at a blood bank, expired or fresh or further stored refrigerated in the laboratory for variable lengths of time, and from fresh or stored refrigerated cord blood. Rubidium, used as a K congener to measure K influx, and the K concentration were determined in the presence and absence of several concentrations (0–150 μg/mL) of negatively charged, spherical 10 nm AgNPs at different time points (0–60 min). Our findings indicate that Creighton AgNPs, independently of the source and in a time‐ and dose‐dependent manner, inhibited Rb influx by ~ 80 % (p < 0.001, n=7) and depleted the cells of K by more than 90 % (p < 0.0001, n = 7), although interindividual differences were observed. In comparison to the Creighton, Lee‐Meisel AgNPs caused a maximum Rb inhibition of ~ 50 % and K loss of ~ 15 % with larger interindividual variability than Creighton AgNPs, albeit in a small sample. The loss of K from HRBCs was entirely accounted for by an increase in K concentration in the extracellular medium. These findings indicate that functionalization of AgNPs has a significant effect on HRBC K homeostasis. Further studies are required to identify the mechanisms underlying the observed changes in HRBC ionic composition.Support or Funding InformationFunded by NSF