Issue 11, 2019

Gd-Metallofullerenol nanoparticles cause intracellular accumulation of PDGFR-α and morphology alteration of fibroblasts

Abstract

Gadolinium-metallofullerenols (Gd@C82(OH)22) are a promising agent for cancer therapy and have shown beneficial effects in regulating the tumor microenvironment with low toxicity. However, the underlying mechanism by which Gd@C82(OH)22 interacts with fibroblasts remains unclear. In order to explore the critical role that activated fibroblasts play in tumorigenesis and fibrosis, we investigated the regulatory effect of Gd@C82(OH)22 in fibroblast activation and oncogenic transformation, and found that the PDGFR-α is an essential molecule in modulating the morphology and functional changes in fibroblasts after Gd@C82(OH)22 treatment. Apart from increasing the PDGFR-α protein level, Gd@C82(OH)22 nanoparticles also significantly increased the protein level of Rab5, which is required for regulating PDGFR-α endosomal recycling. The Rab5-mediated recycling of PDGFR-α maybe attributed to the Gd@C82(OH)22 regulated inhibition of fibroblast activation. Overall, our work demonstrated that Gd@C82(OH)22 nanoparticles can attenuate the PDGF-stimulated phosphorylation of PDGFR-α in fibroblasts and suppress the fibroblast activation by interrupting endosomal recycling. These findings may be contributed to the collagen accumulation for encaging cancer.

Graphical abstract: Gd-Metallofullerenol nanoparticles cause intracellular accumulation of PDGFR-α and morphology alteration of fibroblasts

Supplementary files

Article information

Article type
Paper
Submitted
26 okt 2018
Accepted
07 dec 2018
First published
10 dec 2018

Nanoscale, 2019,11, 4743-4750

Gd-Metallofullerenol nanoparticles cause intracellular accumulation of PDGFR-α and morphology alteration of fibroblasts

J. Tang, M. Guo, P. Wang, J. Liu, Y. Xiao, W. Cheng, J. Gao, W. Hu and Q. R. Miao, Nanoscale, 2019, 11, 4743 DOI: 10.1039/C8NR08667B

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements