Molecular mechanism of Gd@C82(OH)22 increasing collagen expression: Implication for encaging tumor

Jing Liu, Seung gu Kang, Peng Wang, Yue Wang, Xiaonan Lv, Ying Liu, Fei Wang, Zonglin Gu, Zaixing Yang, Jeffrey K. Weber, Ning Tao, Zhihai Qin, Qing Miao, Chunying Chen, Ruhong Zhou, Yuliang Zhao

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Gadolinium-containing fullerenol Gd@C82(OH)22 has demonstrated low-toxicity and highly therapeutic efficacy in inhibiting tumor growth and metastasis through new strategy of encaging cancer, however, little is known about the mechanisms how this nanoparticle regulates fibroblast cells to prison (instead of poison) cancer cells. Here, we report that Gd@C82(OH)22 promote the binding activity of tumor necrosis factor (TNFα) to tumor necrosis factor receptors 2 (TNFR2), activate TNFR2/p38 MAPK signaling pathway to increase cellular collagen expression in fibrosarcoma cells and human primary lung cancer associated fibroblasts isolated from patients. We also employ molecular dynamics simulations to study the atomic-scale mechanisms that dictate how Gd@C82(OH)22 mediates interactions between TNFα and TNFRs. Our data suggest that Gd@C82(OH)22 might enhance the association between TNFα and TNFR2 through a “bridge-like” mode of interaction; by contrast, the fullerenol appears to inhibit TNFα-TNFR1 association by binding to two of the receptor's cysteine-rich domains. In concert, our results uncover a sequential, systemic process by which Gd@C82(OH)22 acts to prison tumor cells, providing new insights into principles of designs of cancer therapeutics.

Original languageEnglish (US)
Pages (from-to)24-36
Number of pages13
JournalBiomaterials
Volume152
DOIs
StatePublished - Jan 2018

Keywords

  • Caging cancer cells
  • Cancer therapeutics
  • Fibrosarcoma cells
  • Gd-metallofullerenol
  • Molecular dynamics
  • TNF receptors

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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