Overview on biological implications of metal oxide nanoparticle exposure to human alveolar A549 cell line

Abstract

Metal oxides (MeOx) are exponentially being used in a wide range of applications and are the largest class of commercially produced nanomaterials. This presents unprecedented human exposure. Thus, understanding nanoparticle induced cellular stress can greatly help design strategies to combat them. Scores of studies have been carried out to understand the effects of MeOx nanoparticle exposure on human alveolar cells, which are highly susceptible to aerosolized matter. There is a huge redundancy of information generated, also, a lack of a comprehensive conglomeration of this information. We have built here in a sincere summary of the cellular responses reported till date as a direct consequence of MeOx nanoparticle exposure on human alveolar (A549) cells. Detailed accounts of cellular morphology modulation, generation of reactive oxygen species (ROS) and oxidative stress, inflammation and cytokine release, genotoxic and epi-genotoxic insults, toxicological trend, nanoparticle internalization, modes of cell death, protein synthesis, and membrane damage among others are discussed. Finally, to aid predictability of the highly dynamic and multifactorial nature of this toxicity, we have hypothesized models that describe the ensuing mechanisms based on common patterns discovered throughout our literature survey.

Evolution of Bioengineered Lung Models: Recent Advances and Challenges in Tissue Mimicry for Studying the Role of Mechanical Forces in Cell Biology

“…Currently, the vast majority of in vitro efficacy, toxicity, and pharmacokinetics studies of the lung are performed using static pulmonary cell models culturing a single cell type under submerged conditions . While this approach is well established, it often lacks predictive power for in vivo/clinical outcome due to nonphysiologic and simplistic cell model conditions and an unknown dose of the test substance delivered to the cells .…”

Quinacrine inhibits GSTA1 activity and induces apoptosis through G1/S arrest and generation of ROS in human non-small cell lung cancer cell lines

“…Quinacrine is directly responsible for the generation of intracellular ROS leading to oxidative stress in cell and causes devastating effects on cellular processes such as DNA damage ( Supplementary Figure 5), endoplasmic reticulum stress etc. These effects trigger the apoptotic process when the damage is beyond the repair capability [37][38][39]. Our results indicate that ROS is generated in a dose dependent manner, which sustains due to inefficient dissolution by GSTs, Superoxide dismuatses and other ROS responsive genes.…”

In Vitro Cytotoxicity Evaluation of the Magnéli Phase Titanium Suboxides (TixO2x−1) on A549 Human Lung Cells

“…This leads to versatile NP-cell interactions and a variety of cellular responses [1]. Numerous investigations have already been conducted that studied cell interactions with various types of NPs, from polymeric NPs [2], lipid-based NPs [3], carbon based NPs [4,5,6], and metal oxide NPs [7,8,9]. Nevertheless, numerous NPs with modified or new properties are being developed every day, and understanding their interactions with cells and cellular responses is an important scientific issue that has to be addressed in order to assure their safe and efficient use [10].…”