Mechanistic paradigms of immunotoxicity, triggered by nanoparticles - a review.

Abstract

Nanoparticles (NPs) possess the ability to penetrate cells and elicit a rapid and targeted immune response, influenced by their distinct physicochemical properties. These particles can engage with both micro and macromolecules, thereby impacting various downstream signaling pathways that may lead to cell death. This review provides a comprehensive overview of the primary mechanisms contributing to the immunotoxicity of both organic and inorganic nanoparticles. The effects of carbon-based nanomaterials (CNMs), including single-walled carbon nanotubes, multi-walled carbon nanotubes, graphene, and metal oxide nanoparticles, on various immune cell types such as macrophages, neutrophils, monocytes, dendritic cells (DCs), antigen-presenting cells (APCs), and RAW 264.7 cells are examined. The immune responses discussed encompass inflammation, oxidative stress, autophagy, and apoptosis. Additionally, the roles of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and IFN-γ, along with JAK/STAT signaling pathways, are highlighted. The interaction of NPs with oxidative stress pathways, including MAPK signaling and Nrf2/ARE signaling, is also explored. Furthermore, the mechanisms by which nanoparticles induce damage to organelles such as lysosomes, the endoplasmic reticulum, exosomes, and Golgi bodies within the immune system are addressed. The review also emphasizes the genotoxic and epigenetic mechanisms associated with the immunotoxicity of NPs. Recent advancements regarding the immunotherapeutic potential of engineered NPs are reported. The roles of autophagy and apoptosis in the immunotoxicity of NPs merit further investigation. In conclusion, understanding how engineered nanoparticles modulate immune responses may facilitate the prevention and treatment of human diseases, including cancer and autoimmune disorders. The potential development of new vaccines utilizing engineered NPs could pave the way for innovative approaches in the field of immunotherapy.