Particle surface functionalization affects mechanism of endocytosis and adverse effects of silver nanoparticles in mammalian kidney cells. Issue 3 (13th September 2022)

• Record Type: Journal Article
• Authors: Beus, Maja; Pongrac, Igor M.; Capjak, Ivona; Ilić, Krunoslav; Vrček, Ena; Ćurlin, Marija; Milić, Mirta; Čermak, Ana Marija Marjanović; Pavičić, Ivan
• Is Part Of: Journal of applied toxicology. Volume 43:Issue 3(2023)
• Page Start: 416
• Page End: 430
• Publication Date: 2022-09-13
• Subjects: cellular uptake -- cytotoxicity -- genotoxicity -- oxidative stress -- PK15 cells; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.4392
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: Silver nanoparticles (AgNPs) show a plethora of possible applications due to their antimicrobial properties. Different coatings of AgNPs are used in order to increase stability, availability, and activity. However, the question about the toxicity after prolonged exposure still remains. Here, we show that different surface coatings affect in vitro toxicity and internalization of AgNPs in porcine kidney (PK15) cells. AgNPs coated with cetyltrimethylammonium bromide (CTAB), poly(vinylpyrrolidone) (PVP), sodium bis(2‐ethylhexyl)‐sulfosuccinate (AOT), poly‐ L ‐lysine (PLL), and bovine serum albumin (BSA) were toxic at the concentration of 10 mg Ag/L and higher. The toxicity increased in the following manner: PVP‐AgNPs < CTAB‐AgNPs < PLL‐AgNPs < AOT‐AgNPs < BSA‐AgNPs. All types of AgNPs were internalized by the PK15 cells in a dose‐dependent manner with greater internalization of AgNPs bearing positive surface charge. Transmission electron microscopy (TEM) experiments showed that AgNPs were located in the lysosomal compartments, while the co‐treatment with known inhibitors of endocytosis pathways suggested macropinocytosis as the preferred internalization pathway. When inside the cell, all types of AgNPs induced the formation of reactive oxygen species while decreasing the concentration of the cell's endogenous antioxidant glutathione. The comet assay indicated possible genotoxicity of tested AgNPs starting at the concentration of 2 mg Ag/L or higher, depending on the surface functionalization. This study demonstrates the toxicity of AgNPs pointing to the importance of biosafety evaluation when developing novel AgNPs‐containing materials. Abstract : Silver nanoparticles (AgNPs) are widely used due to their antimicrobial properties. The present study indicates the effect of AgNP's surface coating on their in vitro toxicity and internalization in kidney cells. AgNPs were toxic at a concentration of 10 ppm and higher. Positively charged AgNPs were internalized to a greater extent than negative. Inside the cell, AgNPs were located in lysosomal compartments with macropinocytosis as the preferred internalization pathway. All AgNPs induced oxidative stress while comet assay revealed possible genotoxicity.