TY - JOUR
T1 - Polyhydroxylated fullerenols regulate macrophage for cancer adoptive immunotherapy and greatly inhibit the tumor metastasis
AU - Tang, Jinglong
AU - Chen, Zhiyun
AU - Sun, Baoyun
AU - Dong, Jinquan
AU - Liu, Jing
AU - Zhou, Huige
AU - Wang, Liming
AU - Bai, Ru
AU - Miao, Qing
AU - Zhao, Yuliang
AU - Chen, Chunying
AU - Liu, Ying
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China ( U1532122 , 31571027 , 21320102003 ), the Ministry of Science Technology of China ( 2012CB934003 ), International Science & Technology Cooperation Program of the Ministry of Science Technology of China ( 2013DFG32340 , 2014DFG52500 ), Danish Strategic Research Foundation on Project ElectroMed ( 11-115313 ), National Major Scientific Instruments Development Project ( 2011YQ03013406 ) and the National Science Fund for Distinguished Young Scholars ( 11425520 ).
Publisher Copyright:
© 2015 Elsevier Inc.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Adoptive immunotherapy is a highly effective approach for cancer treatment. Several potential adoptive immunotherapies have high (though reversible) toxicities with disappointing results. Polyhydroxylated fullerenols have been demonstrated as promising antitumor drugs with low toxicities. In this study, we investigate whether polyhydroxylated fullerenols (C60(OH)22 and Gd@C82(OH)22) contribute to cancer immunotherapy by regulating macrophages. Our results show that fullerenols treatment enhances mitochondrial metabolism, phagocytosis and cytokine secretion. Moreover, activated macrophages inhibit the growth of several cancer cell types. It is likely that this inhibition is dependent on an NF-κB-mediated release of multiple cytokines. Using a lung metastasis model, we also show that autologous macrophages greatly suppress cancer cell metastasis to lung when they are activated by C60(OH)22 and Gd@C82(OH)22. More importantly, Gd@C82(OH)22 are shown to have stronger ability than C60(OH)22 to improve the macrophage function, which shed light on the rational design for nanomedicine and clinical application.
AB - Adoptive immunotherapy is a highly effective approach for cancer treatment. Several potential adoptive immunotherapies have high (though reversible) toxicities with disappointing results. Polyhydroxylated fullerenols have been demonstrated as promising antitumor drugs with low toxicities. In this study, we investigate whether polyhydroxylated fullerenols (C60(OH)22 and Gd@C82(OH)22) contribute to cancer immunotherapy by regulating macrophages. Our results show that fullerenols treatment enhances mitochondrial metabolism, phagocytosis and cytokine secretion. Moreover, activated macrophages inhibit the growth of several cancer cell types. It is likely that this inhibition is dependent on an NF-κB-mediated release of multiple cytokines. Using a lung metastasis model, we also show that autologous macrophages greatly suppress cancer cell metastasis to lung when they are activated by C60(OH)22 and Gd@C82(OH)22. More importantly, Gd@C82(OH)22 are shown to have stronger ability than C60(OH)22 to improve the macrophage function, which shed light on the rational design for nanomedicine and clinical application.
KW - Adoptive immunotherapy
KW - Cancer
KW - Fullerenol
KW - Macrophage
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U2 - 10.1016/j.nano.2015.11.021
DO - 10.1016/j.nano.2015.11.021
M3 - Article
C2 - 26733256
AN - SCOPUS:84961279249
VL - 12
SP - 945
EP - 954
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
SN - 1549-9634
IS - 4
ER -