Cell membrane damage and protein interaction induced by copper containing nanoparticles—Importance of the metal release process

Abstract

Cu-containing nanoparticles are used in various applications in order to e.g. achieve antimicrobial activities and to increase the conductivity of fluids and polymers. Several studies have reported on toxic effects of such particles but the mechanisms are not completely clear. The aim of this study was to investigate the interactions between cell membranes and well-characterized nanoparticles of CuO, Cu metal, a binary Cu-Zn alloy and micron-sized Cu metal particles. This was conducted via in vitro investigations of the effects of the nanoparticles on (i) cell membrane damage on lung epithelial cells (A549), (ii) membrane rupture of red blood cells (hemolysis), complemented by (iii) nanoparticle interaction studies with a model lipid membrane using quartz crystal microbalance with dissipation monitoring (QCM-D). The results revealed that nanoparticles of the Cu metal and the Cu-Zn alloy were both highly membrane damaging and caused a rapid (within 1h) increase in membrane damage at a particle mass dose of 20 μg/mL, whereas the CuO nanoparticles and the micron-sized Cu metal particles showed no such effect. At similar nanoparticle surface area doses, the nano and micron-sized Cu particles showed more similar effects. The commonly used LDH (lactate dehydrogenase) assay for analysis of membrane damage was found impossible to use due to nanoparticle-assay interactions. None of the particles induced any hemolytic effects on red blood cells when investigated up to high particle concentrations (1mg/mL). However, both Cu and Cu-Zn nanoparticles caused hemoglobin aggregation/precipitation, a process that would conceal a possible hemolytic effect. Studies on interactions between the nanoparticles and a model membrane using QCM-D indicated a small difference between the investigated particles. Results of this study suggest that the observed membrane damage is caused by the metal release process at the cell membrane surface and highlight differences in reactivity between metallic nanoparticles of Cu and Cu-Zn and nanoparticles of CuO.

Evaluation of Curcumin Capped Copper Nanoparticles as Possible Inhibitors of Human Breast Cancer Cells and Angiogenesis: a Comparative Study with Native Curcumin

“…Our results are in agreement with the previous report describing the nonsignificant hemolytic activity of CU at 0.5-100 μM concentrations (40). Almost similar kind of results are reported for a variety of copper-based particles such as nano-and micron-sized copper metal particles, a nano-sized binary copper-zinc alloy, and copper oxide nanoparticles (56).…”

Value of phagocyte function screening for immunotoxicity of nanoparticles in vivo

“…However, it should not be forgotten that metal and metal oxide release ions which can interact with proteins and induce inflammation. 16 Nevertheless, the NPs mentioned in this review form a more homogeneous group than nanocarriers for drug delivery, which consist of different materials and possess different surface charges and functionalization. Polystyrene (PS) particles are included in this review because they are often used as model particles for nonbiodegradable NPs.…”

Effect of Zinc Oxide and Titanium Dioxide Nanoparticles on Supported Lipid Bilayers

“…BLMs as a model system are of great importance for improving our understanding of cell interaction with environment, various disease mechanism and membrane properties for drug screening purposes. Important area of nanomedicine research is the interaction of nanoparticles with cell and a possible toxicity [1][2][3][4][5]. Apart from their mechanical function as a cell wall, lipid membrane performs a function of a transfer mechanism for molecules diffusing through the membrane.…”