The impact of receptor recycling on the exocytosis of αvβ3 integrin targeted gold nanoparticles
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Yanan Cui1,2,3, Xiaoning Song2, Suxin Li2, Bing He2, Lan Yuan2, Wenbing Dai2, Hua Zhang2, Xueqing Wang2, Bin Yang5, Qiang Zhang1,2,4
1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
2Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
3School of Pharmacy, Jining Medicinal University, Jining 272067, China
4State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China
5Institute of Biomedicine and National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Qiang Zhang, email: email@example.com
Wenbing Dai, email: firstname.lastname@example.org
Keywords: gold nanoparticles, αvβ3 integrin, receptor-mediated endocytosis, receptor-mediated exocytosis, active targeting drug delivery
Received: January 02, 2017 Accepted: March 29, 2017 Published: April 08, 2017
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.
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