Abstract
Increasing biomedical applications of iron oxide nanoparticles (IONPs) in academic and commercial settings have alarmed the scientific community about the safety and assessment of toxicity profiles of IONPs. The great amount of diversity found in the cytotoxic measurements of IONPs points toward the necessity of careful characterization and quantification of IONPs. The present document discusses the major developments related to in vitro and in vivo toxicity assessment of IONPs and its relationship with the physicochemical parameters of IONPs. Major discussion is included on the current spectrophotometric and imaging based techniques used for quantifying, and studying the clearance and biodistribution of IONPs. Several invasive and non-invasive quantification techniques along with the pitfalls are discussed in detail. Finally, critical guidelines are provided to optimize the design of IONPs to minimize the toxicity.
Highlights
The commercial use of engineered nanoparticles (NPs) has increased extensively in recent years to include applications in areas such as advanced nanoelectronics, optics, enhanced automation and robotics, nanostructured chemical catalysts, textile, oil and gas industries [1,2]
The current review aims to explain the correlation between the mechanism of toxicity of iron oxide nanoparticles (IONPs) and major physicochemical factors responsible for in vitro/in vivo toxicity
An enormous amount of cytotoxic studies appeared in the literature to improve the current understanding of toxicity of IONPs
Summary
The commercial use of engineered nanoparticles (NPs) has increased extensively in recent years to include applications in areas such as advanced nanoelectronics, optics, enhanced automation and robotics, nanostructured chemical catalysts, textile, oil and gas industries [1,2]. Several research studies aiming to investigate the IONPs-induced ROS production proposed a few mechanisms such as peroxidase-like activity of IONPs promoted in acidic environment of lysosomes, interaction of iron ions with mitochondria, and activation of cell signaling [31]. These studies involved IONPs synthesized by different techniques, coating agents, types of tissues/cells, and cytotoxicity assays Due to this diversity, it has been extremely difficult to assign a definite toxicity profile that can be followed while choosing the proper IONPs. Several reports discussed the higher toxicity of bare IONPs than coated IONPs; some research studies have found the toxicity of bare IONPs to be less than that of the (oleate) coated IONPs. Oleate itself did not show any cytotoxicity, which shows that the toxicity might have been associated with the interaction and cellular uptake of oleate coated IONPs [39]. Incorporating a layer on bare IONPs can certainly reduce the toxicity levels by reducing the oxidative stress and alterations in iron homeostasis [40], but the direct role of surface passivation of IONPs has not been clearly understood. Some researchers speculated that the extra layer reduced leaching of iron ions and the lysosomal degradation of iron ions [41]
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