Toxicity mechanism of nanomaterials: Focus on endoplasmic reticulum stress

Over the years, although the broad application of nanomaterials has not brought convenience to people's life, growing concern surrounds their safety. Recently, much emphasis has been placed on exploring the toxicity mechanism of nanoparticles. Currently established toxic mechanisms include oxidative stress, inflammatory response, autophagy, and DNA damage. In recent years, endoplasmic reticulum stress (ERS) has gained widespread attention as another toxic mechanism of nanomaterials. It is widely acknowledged that the endoplasmic reticulum (ER) is an important site for protein synthesis, and lipids and Ca⁺ storage, playing an esseential role in the normal operation of the body functions. When the body's internal environment is damaged, the structure and function of the endoplasmic reticulum are destroyed, leading to a series of biological reactions called endoplasmic reticulum stress (ERS.) This paper reviews the mechanism of ERS in nanomaterial-associated toxicity. The process of ERS and its related unfolded protein response were briefly introduced, summarizing the factors affecting the nanoparticle ability to induce ERS and expounding on the changes of ER morphology after exposure to nanoparticles. Finally, the specific role and molecular mechanism of ERS under the action of different nanoparticles were comprehensively analyzed, including the relationship between ERS and inflammation, oxidative stress, lipid metabolism and apoptosis. This review provides a foothold for future studies on the toxic mechanism of nanoparticles, and provides novel insights into the safe application of nanoparticles and the treatment of diseases.