The impact of receptor recycling on the exocytosis of αvβ3 integrin targeted gold nanoparticles.

Among the diverse factors that may influence the therapeutic outcomes, the exocytosis of targeted drug delivery systems (TDDS) and its relationship with the corresponding receptor receive little attentions. In this study, cRGDfK modified gold nanoparticles (cRGDfK-PEG-AuNPs) were synthesized, and their cellular transportation including endocytosis and exocytosis, as well as the potential relations with αvβ3 integrin were carefully studied. The results showed that the enhanced and fast internalization of cRGDfK-PEG-AuNPs into U87 cells was associated with the high expression level of αvβ3 integrin. Importantly, the significant exocytosis of cRGDfK-PEG-AuNPs, but not the PEG conjugated gold nanoparticles (PEG-AuNPs), was found under the in vivo-simulated serum containing conditions. Interestingly, the exocytosis kinetics of nanoparticles was demonstrated to be tightly related with the recycling of the αvβ3 integrin, although the exocytosis of cRGDfK-PEG-AuNPs slightly lagged behind the receptor recycling. In effect, our findings uncover a new underlying behavior of receptor mediated TDDS and have implication for their rational design and application in the future.