Metallofullerenol Inhibits Cellular Iron Uptake by Inducing Transferrin Tetramerization

Jinxia Li, Xueqing Xing, Baoyun Sun, Yuliang Zhao, Zhonghua Wu

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Herein, A549 tumor cell proliferation was confirmed to be positively dependent on the concentration of Fe3+ or transferrin (Tf). Gd@C82(OH)22 or C60(OH)22 effectively inhibited the iron uptake and the subsequent proliferation of A549 cells. The conformational changes of Tf mixed with FeCl3, GdCl3, C60(OH)22 or Gd@C82(OH)22 were obtained by SAXS. The results demonstrate that Tf homodimers can be decomposed into monomers in the presence of FeCl3, GdCl3 or C60(OH)22, but associated into tetramers in the presence of Gd@C82(OH)22. The larger change of SAXS shapes between Tf+C60(OH)22 and Tf+FeCl3 implies that C60(OH)22 is bound to Tf, blocking the iron-binding site. The larger deviation of the SAXS shape from a possible crystal structure of Tf tetramer implies that Gd@C82(OH)22 is bound to the Tf tetramer, thus disturbing iron transport. This study well explains the inhibition mechanism of Gd@C82(OH)22 and C60(OH)22 on the iron uptake and the proliferation of A549 tumor cells and highlights the specific interactions of a nanomedicine with the target biomolecules in cancer therapy.

Original languageEnglish (US)
Pages (from-to)2646-2651
Number of pages6
JournalChemistry - An Asian Journal
Volume12
Issue number20
DOIs
StatePublished - Oct 18 2017

Keywords

  • cancer therapy
  • iron uptake
  • nanomedicine
  • small-angle X-ray scattering
  • transferrin

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

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