Mechanisms of nanoparticle-induced autophagy disruption and its crosstalk with ferroptosis.

With the rapid development of nanotechnology, nanoparticles that are typically defined as particulate materials with at least one dimension between 1 and 100 nm have found widespread applications in various fields, particularly in biomedicine. Nanoparticles can induce significant physiological disturbances, including dysregulation of autophagy and ferroptosis. As a vital cellular quality control mechanism, autophagy plays a dual role in cell survival and death while maintaining physiological homeostasis. Growing evidence indicates that autophagy-mediated ferroptosis contributes to various human diseases, making it crucial to understand how nanoparticles affect these interconnected processes for safe biomedical applications. Nanoparticles perturb autophagy through multiple mechanisms: (1) cellular adhesion and internalization of nanoparticles can interfere with autophagy-related proteins; (2) nanoparticle-induced organelle damage and DNA damage activate autophagy pathways; and (3) cellular uptake of nanoparticles may cause lysosomal dysfunction, leading to impaired autophagosome degradation. These interconnected mechanisms collectively contribute to autophagy dysregulation. This review summarizes current knowledge on nanoparticle-induced autophagy and its role in triggering ferroptosis, with a particular focus on biomedical applications. A comprehensive understanding of how nanoparticles modulate autophagy and how autophagy subsequently induces ferroptosis will significantly advance the development of nanoparticle-based biomedical technologies.