Immunological effects of iron oxide nanoparticles and iron-based complex drug formulations: Therapeutic benefits, toxicity, mechanistic insights, and translational considerations

Abstract

Nanotechnology offers several advantages for drug delivery. However, there is the need for addressing potential safety concerns regarding the adverse health effects of these unique materials. Some such effects may occur due to undesirable interactions between nanoparticles and the immune system, and they may include hypersensitivity reactions, immunosuppression, and immunostimulation. While strategies, models, and approaches for studying the immunological safety of various engineered nanoparticles, including metal oxides, have been covered in the current literature, little attention has been given to the interactions between iron oxide-based nanomaterials and various components of the immune system. Here we provide a comprehensive review of studies investigating the effects of iron oxides and iron-based nanoparticles on various types of immune cells, highlight current gaps in the understanding of the structure-activity relationships of these materials, and propose a framework for capturing their immunotoxicity to streamline comparative studies between various types of iron-based formulations.

Biologically Targeted Magnetic Hyperthermia: Potential and Limitations

“…MIONs can mediate toxicity through several mechanisms that all have to be taken into account when evaluating their safety. Most intracellular toxicity is caused by generation of reactive oxygen species whereas in vivo disturbances of blood clotting, iron homeostasis and macrophage function, as well as organ toxicities, are additional considerations (Ilinskaya and Dobrovolskaia, 2013 ; Wu et al, 2014 ; Wei et al, 2016 ; Shah and Dobrovolskaia, 2018 ). A more detailed discussion of MION toxicity can be found in specialized review articles (Reddy et al, 2012 ; Liu et al, 2013 ; Arami et al, 2015 ).…”

Improving Tumor Retention of Effector Cells in Adoptive Cell Transfer Therapies by Magnetic Targeting

“…In general, MNPs do not cause notable toxicity in different immune cell types, with high cell viability percentages often observed [86]. MNP toxicity usually occurs mainly when high doses and prolonged exposure times are used [87,88] or in the presence of certain coatings [89]. Besides, there are several studies demonstrating the low toxicity of MNPs in both human and murine T and NK cell lines and in primary T and NK cells [75,78,80,[89][90][91][92][93][94][95][96][97][98][99].…”

Iron oxide nanoparticle-induced hematopoietic and immunological response in rats

“…34 Production of reactive oxygen species can be induced by nano-materials as nanomaterials are able to reach mitochondria and hence may induce inammatory response in activated macrophages. 35 Microarray analysis revealed that gene responsible for oxidative stress and inammatory responses undergo for reprogramming in IONPs treated mouse macrophages. 36 We therefore speculate that IONPs-induced ROS activates NF-kB, which subsequently leads to release of pro-inammatory cytokines.…”