Nanoparticle-Mediated Modulation of Bulk and Selective Autophagy: From Mechanistic Activation to Clinical Perspectives

Autophagy is an evolutionarily conserved catabolic process essential for maintaining cellular homeostasis in physiological and pathological conditions. Dysregulation of autophagy can lead to various diseases, including neurodegenerative disorders, cancer, and infections. Given its critical role in cellular health, autophagy modulation has emerged as a promising therapeutic strategy to prevent disease onset, slow progression, or mitigate severity. Over the past decade, nanoparticles have shown significant potential in autophagy modulation due to their ability to facilitate targeted delivery, enhance the stability of therapeutic agents, and enable the controlled release of autophagy-inducing molecules. Additionally, certain nanoparticles, such as lipid-based, polymeric, and metallic systems, can directly influence autophagic pathways. This review provides a detailed analysis of the molecular mechanisms through which nanoparticles induce bulk autophagy and their role in facilitating selective autophagy by targeting specific cellular cargo for degradation. It highlights the importance of nanoparticle design in the induction of autophagy. It also discusses the challenges associated with nanoparticle-mediated autophagy induction in clinical translation. Future perspectives focus on optimizing nanoparticle systems to achieve targeted and effective autophagy modulation, advancing their clinical utility for therapeutic interventions in autophagy-related diseases.