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受体循环对靶向αvβ3整合素的金纳米颗粒胞吐作用的影响。

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

作者信息

Cui Yanan, Song Xiaoning, Li Suxin, He Bing, Yuan Lan, Dai Wenbing, Zhang Hua, Wang Xueqing, Yang Bin, Zhang Qiang

机构信息

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.

Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

出版信息

Oncotarget. 2017 Jun 13;8(24):38618-38630. doi: 10.18632/oncotarget.16955.

DOI:10.18632/oncotarget.16955
PMID:28454098
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5503558/
Abstract

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.

摘要

在可能影响治疗效果的多种因素中，靶向给药系统（TDDS）的胞吐作用及其与相应受体的关系很少受到关注。在本研究中，合成了cRGDfK修饰的金纳米颗粒（cRGDfK-PEG-AuNPs），并仔细研究了它们的细胞转运，包括内吞作用和胞吐作用，以及与αvβ3整合素的潜在关系。结果表明，cRGDfK-PEG-AuNPs在U87细胞中的增强和快速内化与αvβ3整合素的高表达水平有关。重要的是，在含有体内模拟血清的条件下，发现cRGDfK-PEG-AuNPs有明显的胞吐作用，而聚乙二醇共轭金纳米颗粒（PEG-AuNPs）则没有。有趣的是，尽管cRGDfK-PEG-AuNPs的胞吐作用略滞后于受体循环，但纳米颗粒的胞吐动力学被证明与αvβ3整合素的循环密切相关。实际上，我们的研究结果揭示了受体介导的TDDS的一种新的潜在行为，并对其未来的合理设计和应用具有启示意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/ef34b0b8cf3e/oncotarget-08-38618-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/19fd8029a995/oncotarget-08-38618-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/836f33dd3714/oncotarget-08-38618-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/79f57ef07848/oncotarget-08-38618-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/da09efe5f58b/oncotarget-08-38618-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/5f56f21a07a1/oncotarget-08-38618-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/f9ef59ac6c0a/oncotarget-08-38618-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/b5e7832255ec/oncotarget-08-38618-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/ef34b0b8cf3e/oncotarget-08-38618-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/19fd8029a995/oncotarget-08-38618-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/836f33dd3714/oncotarget-08-38618-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/79f57ef07848/oncotarget-08-38618-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/da09efe5f58b/oncotarget-08-38618-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/5f56f21a07a1/oncotarget-08-38618-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/f9ef59ac6c0a/oncotarget-08-38618-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/b5e7832255ec/oncotarget-08-38618-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/567a/5503558/ef34b0b8cf3e/oncotarget-08-38618-g008.jpg

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