Reactive Oxygen Species-Related Nanoparticle Toxicity in the Biomedical Field

Abstract

The unique physicochemical characteristics of nanoparticles have recently gained increasing attention in a diverse set of applications, particularly in the biomedical field. However, concerns about the potential toxicological effects of nanoparticles remain, as they have a higher tendency to generate excessive amounts of reactive oxygen species (ROS). Due to the strong oxidation potential, the excess ROS induced by nanoparticles can result in the damage of biomolecules and organelle structures and lead to protein oxidative carbonylation, lipid peroxidation, DNA/RNA breakage, and membrane structure destruction, which further cause necrosis, apoptosis, or even mutagenesis. This review aims to give a summary of the mechanisms and responsible for ROS generation by nanoparticles at the cellular level and provide insights into the mechanics of ROS-mediated biotoxicity. We summarize the literature on nanoparticle toxicity and suggest strategies to optimize nanoparticles for biomedical applications.

Sensitive SQUID Bio-Magnetometry for Determination and Differentiation of Biogenic Iron and Iron Oxide Nanoparticles in the Biological Samples

“…PEG is a neutral, hydrophilic and biocompatible polymer which improves the dispersion of NPs in water, it improves their bio-distribution and increases blood circulation time [ 30 ]. However, despite the PEG-coating and administration of a low dose of USPIONs, we found elevated production of the superoxide, which was increased in all tissues and organs investigated in this study, similarly as it was found using various types of NPs [ 31 ]. On the other hand, we were unable to unequivocally confirm elevated iron content in the tissues using the histochemical method.…”

Distinct photooxidation-induced cell death pathways lead to selective killing of human breast cancer cells

“…Intriguingly, we have also detected activation of necroptosis only in tumorigenic cells submitted to photooxidation damage. Necroptosis is triggered by perturbations of extracellular or intracellular homeostasis that critically depend on the kinase activities of RIPK1, at least in some settings, RIPK3, and consequent phosphorylation, oligomerization and migration of MLKL (mixed lineage kinase domain-like protein) to the plasma membrane 3,48 . MLKL oligomers form channels on the plasma membrane, leading to high osmotic pressure, water influx, release of intracellular components, and eventual plasma membrane rupture 54 .…”

“…Collectively, our data have provided molecular mechanisms behind a hitherto unexplored therapeutic approach, which have simultaneously activated alternative tumor regulated cell death pathways while preserving the integrity of most of the non-tumorigenic cells. This fact is of fundamental importance since despite all the recent technological improvements, breast cancer still has significantly impacts on global health, being disease recurrence and metastasis the bottleneck for an effective clinical treatment 2,3 . This study contributes to a better understanding of breast cancer susceptibility to photooxidation-induced damage.…”

“…Photodynamic therapy (PDT) has been the focus of several cancer centers as it might represent an important advancement in treatment due to its high but also controlled cytotoxic effect 4 . Additionally, the enhanced antitumor effects combining PDT and chemotherapies have already been demonstrated in preclinical studies on breast cancer 3 . PDT consists in the uptake of a photosensitizer (PS) molecule which, upon excitation by light in a determined wavelength, reacts with oxygen and generates oxidant species (radicals, singlet oxygen, triplet species) in target tissues, leading to photooxidative stress (PhOxS) 5,6 , which results in photodamage of membranes and organelles 7,8 .…”

“…In its advanced stages, when distant organ metastases occur, it is considered incurable with the currently available therapies 2 . The reason being that metastatic lesions are usually multiple, molecular and cellular heterogenous, and resistant to conventional treatments 3 . Thus, effective and safe therapies for this stage of the disease are still needed.…”