Toxic effect of nanoparticles on macrophages

Due to the extensive use of nanoparticles, toxicologists and scientists alike are interested in better understanding their safety profile. The toxic effects of nanoparticles on macrophages, for example, require further research, as these immune cells often first encounter nanoparticles after they enter the body.

Recently Life Science In the study, researchers discussed the molecular changes, as well as the underlying mechanisms, that appear in macrophages after their interaction with nanoparticles.

Study: An in vitro review of nanoparticles attacking macrophages: Cell interactions and death. Image Credit: Kateryna Kon / Shutterstock.com

Background

Nanoparticles can be engineered or natural particles that are smaller than 100 nanometers (nm) in at least one dimension. Over the past few decades, nanotechnology has developed rapidly, which has subsequently increased the demand for nanoparticles such as titanium dioxide, zinc oxide (ZnO), graphene, and smaller quantum dots. These nanoparticles, which are widely used in many industries, including clothing, food, and cosmetics, have small sizes and excellent optical properties.

The dual path exposure is the result of the wide application of nanoparticles. Nanoparticles can enter the human body through skin contact, inhalation, or ingestion, as well as intravenous injection. After deposition, nanoparticles can be absorbed and distributed throughout the body by epithelial cells, lung macrophages, and various other cell types.

Once the nanoparticles enter the body, they accumulate in their target organs, such as the spleen, liver, or kidneys, with possible distribution to the heart and brain. Recent studies have described in vitro toxicity of most of the nanoparticles, which has increased the urgency in addressing the safety profile of these particles.

Macrophages, which belong to the immune and mononuclear phagocytic system (MPS), are important members of the immune response, as they phagocytize about 95% of invading nanoparticles. However, macrophages are susceptible to foreign nanoparticles and, consequently, are partially involved in the tissue injury process.

Study findings

Nanoparticles internalized by macrophages or targeting macrophages can induce cytotoxicity through generation of functional damage and reduction of cell viability.

Currently in vitro The macrophage model mainly considers alveolar macrophages, microglia, and hepatic macrophages. In the context of the KUP5 and Hepa1-6 cell lines, significant cytotoxicity has been reported after exposure to silver (Ag), copper oxide (CuO), vanadium pentoxide (V₂HI₅), and ZnO nanoparticles in both cell lines.

Physicochemical factors influencing macrophage cytotoxicity after nanoparticle exposure have also been assessed. For this purpose, the size, shape, charge and surface properties of nanoparticles can influence their absorption and cell interactions.

Size is considered to be an important factor in the absorption of nanoparticles. Generally, the smaller the size, the greater the cytotoxicity.

Nanoparticles also come in a variety of shapes, such as rings and tubes, with spherical nanoparticles most easily internalized by cells. In particular, spherical nanoparticles are less cytotoxic, which contradicts the popular belief that the most toxic nanoparticles are easily internalized.

The surface modification of the nanoparticles also contributes to their overall cytotoxicity. For example, silica coating significantly improves the biocompatibility of gadolinium oxide nanoparticles and, as a result, reduces their cytotoxicity.

Nanoparticle-mediated toxic effects appear in the form of genetic damage, oxidative stress, and inflammatory responses. In addition, there are five key aspects related to cellular changes and interactions, which include internalization by macrophages, DNA damage, cell death, as well as production of reactive oxygen species (ROS) and cytokines.

Cell internalization is the process of entry of foreign particles into the cell. Thus, the process is influenced by the physical and chemical properties of the surface molecules. The invading nanoparticles are mainly digested by macrophages through their phagocytic activity.

The mechanism of ROS production differs across nanoparticles, with mitochondria being the main source of ROS production. Importantly, not all nanoparticles induce ROS production, with the majority of metal nanoparticles producing toxicity through induction of hydroxyl reactions via Fenton-type reactions.

The mechanism of nanoparticles inducing cytotoxicity to macrophages is similar to the classical toxic mechanism of nanoparticles, namely the production and release of pro-inflammatory cytokines and the subsequent inflammatory response. Nanoparticles can also induce DNA damage through direct contact or through oxidative stress and inflammatory responses.

Cell death is the most detrimental cell change, which can take the form of apoptosis, known as programmed death, autophagy, and necrosis, or non-programmed death. Different types of nanoparticles induce different types of cell death.

Conclusion

In the current study, the researchers summarize the toxic effects of nanoparticles on macrophages in vitro and describe the cellular changes that occur after this interaction. Taken together, macrophage toxicity due to nanoparticles is mainly demonstrated through nanoparticle internalization, inflammatory response, oxidative stress, cell death, and DNA damage.

In the future, researchers should investigate non-classical toxicity mechanisms and explore further in vivo macrophage nanoparticle toxicity.

Journal reference:

• Niu, Y. and Tang, M. (2022) In vitro review of nanoparticles attacking macrophages: Interactions and cell death. Life Science. doi:10.1016/j.lfs.2022.120840

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