Nanotoxic Effects of Silver Nanoparticles on Normal HEK-293 Cells in Comparison to Cancerous HeLa Cell Line

Abstract

Purpose Biomimetic approaches for the synthesis of silver nanoparticles (AgNPs) had created a substantial impression among the research community that focuses on nano-bio interactions. In this study, an eco-friendly method using Rhizophora apiculata aqueous leaf extract as a reductant-rich hydrosol was followed to synthesize AgNPs and test its cytotoxicity. Methods To optimise the parameters for the synthesis of AgNPs, central composite design based on response surface methodology was used. The particles synthesized at a nano-scale were characterized in our previously published report. The present report further characterizes the nanoparticles by X-ray diffraction, SEM and TEM at varying sites and magnifications. The characterized AgNPs were tested for their cytotoxic effects on HEK-293 and HeLa cells. Results The cytotoxicity on the cell lines was dose-dependent. At a concentration of 2.5 μL/mL of the AgNPs-containing hydrosol, 100% inhibition of HEK-293 cells and 75% inhibition of the HeLa cells were observed. The IC 50 value for AgNPs on HEK-293 was 0.622 µL/mL (12.135 ng), whereas, for HeLa cells, it was 1.98 µL/mL (38.629 ng). Conclusion The nanoparticles were three-fold toxic towards the HEK-293 cells in comparison to the HeLa cells. Therefore, the therapeutic index is low for R. apiculata derived AgNPs on HeLa cells when tested in comparison with the HEK-293 cells. The nanotoxicity profile of the synthesized AgNPs seems more prominent than the nanotherapeutic index. According to our knowledge, this is the first-ever report on the optimization of synthesis of AgNPs using response surface methodology and identifying the therapeutic index of mangrove leaf-derived AgNPs.

Silver Nanoparticles Stable to Oxidation and Silver Ion Release Show Size-Dependent Toxicity In Vivo

“…Exposure to the two largest particle sizes, 80 and 100 nm, did not result in significant mortality (Figure 3). Overall, this is consistent with the literature, which shows that nanoparticle toxicity in zebrafish is size-dependent, with smaller nanoparticles being more toxic [29,34,35]. The toxicity observed in the studies with shielded AgNPs eliminates the contribution of Ag + to toxicity.…”

“…Similarly, Liu et al (2019) noted that size is a bigger contributor to toxicity than surface coating [34]. However, the stability of coatings used in past research has been much less robust, with toxicity being attributed to changes in stability and aggregation over time [34]. In contrast, this study's coated particles were found to be stable, with negligible dissolution or aggregation beyond the timeframe of the zebrafish exposures.…”

“…For example, morphological and neurological defects are common at high concentrations of AgNPs [31,35]. AgNPs have been shown to accumulate in the tissue of zebrafish (gills, intestines, muscles [34], and head [35]), with smaller nanoparticles causing greater sublethal toxicity in the gills and intestines than larger nanoparticles [34]. For uncoated AgNPs, smaller nanoparticles are internalized more rapidly than larger nanoparticles [35].…”

“…Our study demonstrates a pattern of decreasing toxicity with increasing size of the AgNPs, indicating that, with dissolution prevented, particle size remains an important driver of toxicity. Similarly, Liu et al (2019) noted that size is a bigger contributor to toxicity than surface coating [34]. However, the stability of coatings used in past research has been much less robust, with toxicity being attributed to changes in stability and aggregation over time [34].…”

“…In addition, because silver (Ag) has a strong x-ray attenuation compared to iodinated agents used in imaging, there is significant interest in using AgNPs for x-ray computed tomography imaging and other optical imaging applications [26][27][28][29][30][31]. There is also interest in using them as drug delivery agents for cancer therapy [32][33][34] or rheumatoid arthritis therapy [35]. Consequently, it is expected that the increased production and use will lead to a significant accumulation of AgNPs in wastewater and the environment, potentially increasing exposure to humans [36][37][38].…”