Background: Nanomedicine shows a huge promise for incurable diseases. So
far, more than 50 nanoparticles have been approved by FDA and around 80 nanoformulations
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.
Methods: 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 receptormediated
endocytic pathway. Once residing within the 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.