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

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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

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Publication details

The article was received on 26 Oct 2018, accepted on 07 Dec 2018 and first published on 10 Dec 2018


Article type: Paper
DOI: 10.1039/C8NR08667B
Citation: Nanoscale, 2019, Advance Article

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    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, Advance Article , DOI: 10.1039/C8NR08667B

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