Abstract
Gold nanoparticles (AuNPs) are highly attractive for biomedical applications. Therefore, several in vitro and in vivo studies have addressed their safety evaluation. Nevertheless, there is a lack of knowledge regarding their potential detrimental effect on human kidney. To evaluate this effect, AuNPs with different sizes (13 nm and 60 nm), shapes (spheres and stars), and coated with 11-mercaptoundecanoic acid (MUA) or with sodium citrate, were synthesized, characterized, and their toxicological effects evaluated 24 h after incubation with a proximal tubular cell line derived from normal human kidney (HK-2). After exposure, viability was assessed by the MTT assay. Changes in lysosomal integrity, mitochondrial membrane potential (ΔΨm), reactive species (ROS/RNS), intracellular glutathione (total GSH), and ATP were also evaluated. Apoptosis was investigated through the evaluation of the activity of caspases 3, 8 and 9. Overall, the tested AuNPs targeted mainly the mitochondria in a concentration-dependent manner. The lysosomal integrity was also affected but to a lower extent. The smaller 13 nm nanospheres (both citrate- and MUA-coated) proved to be the most toxic among all types of AuNPs, increasing ROS production and decreasing mitochondrial membrane potential (p ≤ 0.01). For the MUA-coated 13 nm nanospheres, these effects were associated also to increased levels of total glutathione (p ≤ 0.01) and enhanced ATP production (p ≤ 0.05). Programmed cell death was detected through the activation of both extrinsic and intrinsic pathways (caspase 8 and 9) (p ≤ 0.05). We found that the larger 60 nm AuNPs, both nanospheres and nanostars, are apparently less toxic than their smaller counter parts. Considering the results herein presented, it should be taken into consideration that even if renal clearance of the AuNPs is desirable, since it would prevent accumulation and detrimental effects in other organs, a possible intracellular accumulation of AuNPs in kidneys can induce cell damage and later compromise kidney function.
Highlights
Gold nanoparticles (AuNPs) present a wide range of biomedical applications firstly due to their plasmonic properties and apparently low toxicity compared to other inorganic nanoparticles, and secondly, due to their excellent colloidal stability, facile manipulation, and their nontoxic and easy synthesis methods [1,2]
We found that the larger 60 nm AuNPs, both nanospheres and nanostars, are apparently less toxic than their smaller counter parts
The few AuNPs nephrotoxicity studies that have been published focused on a reduced number of samples, usually just two different sized nanospheres with the same capping, that are normally not preferred for biomedical applications [13,14]
Summary
Gold nanoparticles (AuNPs) present a wide range of biomedical applications firstly due to their plasmonic properties and apparently low toxicity compared to other inorganic nanoparticles, and secondly, due to their excellent colloidal stability, facile manipulation, and their nontoxic and easy synthesis methods [1,2]. The vast majority of the in vitro and in vivo studies regarding the toxicity of AuNPs focus on their main target organ, the liver, and only few take into consideration other organs such as the spleen, lungs, or intestine Among these studies, several have associated the exposure to AuNPs with toxicity and reported increased reactive oxygen species production, mitochondrial and lysosomal damage, inflammation, autophagy, DNA damage, and even apoptosis or necrosis [7,8]. Several have associated the exposure to AuNPs with toxicity and reported increased reactive oxygen species production, mitochondrial and lysosomal damage, inflammation, autophagy, DNA damage, and even apoptosis or necrosis [7,8] These studies raise concern regarding the effect of AuNPs on other organs when they are intended for biomedical applications, since they are not biodistributed only to the liver, but can reach other organs, including the kidney [6,9,10]. The few AuNPs nephrotoxicity studies that have been published focused on a reduced number of samples, usually just two different sized nanospheres with the same capping, that are normally not preferred for biomedical applications (i.e., ultrasmall nanoparticles or particles larger than 100 nm) [13,14]
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