Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles

Abstract

Nanomaterials have gained a rapid increase in use in a variety of applications that pertain to many aspects of human life. The majority of these innovations are centered on medical applications and a range of industrial and environmental uses ranging from electronics to environmental remediation. Despite the advantages of NPs, the knowledge of their toxicological behavior and their interactions with the cellular machinery that determines cell fate is extremely limited. This review is an attempt to summarize and increase our understanding of the mechanistic basis of nanomaterial interactions with the cellular machinery that governs cell fate and activity. We review the mechanisms of NP-induced necrosis, apoptosis and autophagy and potential implications of these pathways in nanomaterial-induced outcomes. Abbreviations: Ag, silver; CdTe, cadmium telluride; CNTs, carbon nanotubes; EC, endothelial cell; GFP, green fluorescent protein; GO, graphene oxide; GSH, glutathione; HUVECs, human umbilical vein endothelial cells; NP, nanoparticle; PEI, polyethylenimine; PVP, polyvinylpyrrolidone; QD, quantum dot; ROS, reactive oxygen species; SiO, silicon dioxide; SPIONs, superparamagnetic iron oxide nanoparticles; SWCNT, single-walled carbon nanotubes; TiO, titanium dioxide; USPION, ultra-small super paramagnetic iron oxide; ZnO, zinc oxide.

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

“…With respect to AOPs, this review demonstrated that autophagy and ROS production elicited by NPs appeared to be critical responses to toxicity, as autophagy is a basic stress response and a potential regulator of toxicity. Undoubtedly, the autophagic effects of NPs are highly dependent on their physicochemical characterization [51]. Some NPs can induce both autophagy blockage and autophagic flux in different testing systems.…”

“…Some NPs can induce both autophagy blockage and autophagic flux in different testing systems. Autophagy dysfunction can lead to the accumulation of damaged DNA, proteins, and organelles that in turn increase the risk of cancer, neurodegenerative diseases, and reproductive dysfunction [51]. Effective risk assessment of NPs depends on in vitro testing strategies and relevant non-mammalian models with sufficient sensitivity to these substances.…”

“…It is also likely that autophagy induction by nanomaterials is the result of an attempt by the cell to degrade what is perceived as foreign or aberrant, similar to cellular action against bacteria and other pathogens. As discussed above, nanoparticles are commonly observed within the autophagosomes compartment, suggesting that the activation of autophagy is triggered by the attempt to sequester and degrade materials that enter into the cytoplasm [50,51]. Cytoplasmic nanoparticles undergo ubiquitination and are co-localized with polyubiquitin complexes that are then translocated to the autophagosomes by p62 [52].…”

“…Zhang et al indicated that TiO 2 NPs entered trophoblast HTR-8/SVneo cells and were distributed primarily to lysosomes, where they ultimately induced autophagy in the cells [152]. Thus, food NPs could trigger autophagy blockage and lead to the accumulation of damaged ER and mitochondria and the production of ROS, resulting in further cellular damage such as NLRP3 inflammasome activation [51]. These findings provide insight into autophagy and may account for the early and specific toxicity-inducing mechanisms of NPs.…”

Harnessing Calcium‐Oxalate‐ (CaOx‐) Nanocrystal‐Induced Prodeath Autophagy for Attenuating Human Renal Proximal Tubular Epithelial Cell Injury

“…However, the role of autophagy in CaOx kidney stones remains largely unknown. Moreover, it has been recently documented that nanomaterials could induce cell death through the crosstalk between autophagy and apoptosis, the two main mechanisms of programmed cell death . Thus, this study aims to investigate the occurrence of autophagy induced by CaOx nanocrystals in a human renal proximal tubular epithelial cell line HK‐2.…”