Metallofullerenol Inhibits Cellular Iron Uptake by Inducing Transferrin Tetramerization.

Herein, A549 tumor cell proliferation was confirmed to be positively dependent on the concentration of Fe or transferrin (Tf). Gd@C (OH) or C (OH) effectively inhibited the iron uptake and the subsequent proliferation of A549 cells. The conformational changes of Tf mixed with FeCl , GdCl , C (OH) or Gd@C (OH) were obtained by SAXS. The results demonstrate that Tf homodimers can be decomposed into monomers in the presence of FeCl , GdCl or C (OH) , but associated into tetramers in the presence of Gd@C (OH) . The larger change of SAXS shapes between Tf+C (OH) and Tf+FeCl implies that C (OH) 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@C (OH) is bound to the Tf tetramer, thus disturbing iron transport. This study well explains the inhibition mechanism of Gd@C (OH) and C (OH) 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.