Combined Effect of Nanoparticles of Silver and Silica to HeLa Cells: Synergistic Internalization and Toxicity.

Abstract

The wide range of applications and the enormous production of nanomaterials have raised the possibility that humans may simultaneously contact with various nanomaterials through multiple routes. Although numerous toxicity studies have been conducted on the toxicity of nanomaterials, knowledge of the combined toxicity of nanomaterials remains limited. Herein, the combined toxic effects of the two types of the most widely used nanomaterials, silver and silica, were studied on HeLa cells. In addition, considering there may have possible interplay between nanoparticles of different sizes, two different-sized silica nanoparticles (SNPs) were used. The results indicate that compared with individual exposure, the combined exposure to 35 nm silver nanoparticles (Ag35) and 40 nm or 120 nm SNPs (SNP40 or SNP120) at individual non-toxic concentrations causes more severe cytotoxicity, manifested by the ROS overgeneration, decreased mitochondrial membrane potential and ATP level, and increased apoptosis/necrosis. The internalized Ag35 and its dissolved Ag ions that are delivered into cells by adsorbing on SNPs are identified as the primary contributors to the combined toxicity. Although the cytotoxicity of the mixed Ag35 and SNP40 is comparable to that of the mixed Ag35 and SNP120, there are noticeable differences in their intracellular contents and their subcellular locations due to size effects. This study provides in-depth insights into the combined toxicity of inorganic nanoparticles and highlights the importance of the size effect of nanoparticles in their nanotoxicity assessment.