Background: Nanomedicine casts a huge promise for uncurable diseases. So far, more than 50 nanoparticles have been approved by FDA and around 80 nano-formulations are currently in clinical trials. Nanoparticles possess several advantages over traditional drugs, including higher biocompatibility and bioavailability. One of the challenges for their wide application is insufficient understanding of the molecular network related to internalization of particles and intracellular release of cargos.
Objective: This article aims to review the interactions between nanoparticles, vesicle transportation and autophagy pathways. The underlying molecular machinery is also discussed.
Method: For each step of the vesicle trafficking and autophagy, details of signaling pathways are described for a better understanding of the interactions between delivery vehicles and biomolecules within the cell.
Conclusion: The selection of cellular uptake route mainly depends on physical characteristics of nanoparticles. For nanoparticles modified with ligands, they undergo receptor-mediated endocytic pathway. Once reside within cells, cargos are released after disruption of endosomes, a mechanism called ‘proton sponge effect’. Besides, internalized nanoparticles either can be exocytosized, or they initiate the autophagy response, affecting the intracellular distribution of drugs.