TY - JOUR
T1 - Metallofullerenol Inhibits Cellular Iron Uptake by Inducing Transferrin Tetramerization
AU - Li, Jinxia
AU - Xing, Xueqing
AU - Sun, Baoyun
AU - Zhao, Yuliang
AU - Wu, Zhonghua
N1 - Funding Information:
This work was financially supported by the Ministry of Science and Technology of China (Grant No. 2017YFA0403000), and the National Natural Science Foundation of China (Grant Nos. 21301176, 11405199, U1532105, U1432104).
Publisher Copyright:
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/10/18
Y1 - 2017/10/18
N2 - 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.
AB - 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.
KW - cancer therapy
KW - iron uptake
KW - nanomedicine
KW - small-angle X-ray scattering
KW - transferrin
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U2 - 10.1002/asia.201700910
DO - 10.1002/asia.201700910
M3 - Article
C2 - 28815927
AN - SCOPUS:85031741874
VL - 12
SP - 2646
EP - 2651
JO - Chemistry - An Asian Journal
JF - Chemistry - An Asian Journal
SN - 1861-4728
IS - 20
ER -