Review on the role of autophagy in the toxicity of nanoparticles and the signaling pathways involved

Abstract

As the development of nanotechnology, the application of nanoproducts and the advancement of nanomedicine, the contact of nanoparticles (NPs) with human body is becoming increasingly prevalent. This escalation elevates the risk of NPs exposure for workers, consumers, researchers, and both aquatic and terrestrial organisms throughout the production, usage, and disposal stages. Consequently, evaluating nanotoxicity remains critically important, though standardized assessment criteria are still lacking. The diverse and complex properties of NPs further complicate the understanding of their toxicological mechanisms. Autophagy, a fundamental cellular process, exhibits dual functions—both pro-survival and pro-death. This review offers an updated perspective on the dual roles of autophagy in nanotoxicity and examines the factors influencing autophagic responses. However, no definitive framework exists for predicting NPs-induced autophagy. Beyond the conventional autophagy pathways, the review highlights specific transcription factors activated by NPs and explores metabolic reprogramming. Particular attention is given to NPs-induced selective autophagy, including mitophagy, ER-phagy, ferritinophagy, lysophagy, and lipophagy. Additionally, the review investigates autophagy's involvement in NPs-mediated biological processes such as ferroptosis, inflammation, macrophage polarization, epithelial-mesenchymal transition, tumor cell proliferation and drug resistance, as well as liver and kidney injury, neurotoxicity, and other diseases. In summary, this review presents a novel update on selective autophagy-mediated nanotoxicity and elucidates the broader interactions of autophagy in NPs-induced biological processes. Collectively, these insights offer valuable strategies for mitigating nanotoxicity through autophagy modulation and advancing the development of NPs in biomedical applications.