Summary: | Autophagy plays essential roles in the maintenance of cellular homeostasis by responding to certain stressed conditions such as nutrient deprivation, organelle damage, pathogen infection, and exposure to certain nanomaterials. Through deliberate tuning of the physicochemical properties, the fate of nanomaterial-treated cells is subjected to various cellular toxicity, stress responses, and immune responses, some of which involve various autophagic mechanisms. Beginning from the molecular basis of the autophagy machinery, we will briefly introduce the major understanding of autophagy in inflammation, immunity, cancer metabolism, and therapy. The impact of physicochemical parameters on autophagy induction or inhibition by engineered nanomaterials will be discussed and classified by different working mechanisms. From the perspective of autophagy-targeting cancer therapeutics, we will focus on the advanced nano-formulations for improved drug delivery to impact autophagy in the setting of cancer diseases, as well as designing co-delivery nanomedicine that targets autophagy along with another major cancer pathway with a view to achieving in vivo synergy. Moreover, cancer immunotherapy, aiming at immune cells or checkpoints, is also integrated with autophagy-regulatory components using multiple nano-platforms as an emerging strategy for cancer treatment. Overall, in light of the recent breakthroughs of nanotechnology, targeting autophagy in cancer cells, antigen-presenting cells, or other cell types within tumor microenvironment by precisely designed nanomedicine may provide additional solutions for cancer treatment through autophagy-dependent metabolic regulation or immune pathways. However, one should closely monitor the extent of autophagy alternation and side effects from certain nanoparticles to avoid severe toxic responses.
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