title: Polyhydroxylated fullerenols regulate macrophage for cancer adoptive immunotherapy and greatly inhibit the tumor metastasis.
abstract: 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.
  
  
  BACKGROUND
  The interest in the use of immunotherapy in cancer has rekindled recently. However, many approaches have shown disappointing results. In this study, the authors investigated the effects of polyhydroxylated fullerenol nanoparticles on regulating macrophages for immunotherapy. These positive findings may point a novel way to cancer treatment.
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China; Center for Nanochemistry, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
authors.forename: Jinglong
authors.initials: J
authors.lastname: Tang
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Baoyun
authors.initials: B
authors.lastname: Sun
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Dong
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Huige
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Bai
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China; Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Miao
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Chen
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China. Electronic address: liuy@nanoctr.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D037741:Fullerenes / Q000008:administration & dosage* / Q000009:adverse effects; D005682:Gadolinium / Q000737:chemistry; D006801:Humans; D016219:Immunotherapy, Adoptive; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D037741:Fullerenes; C108127:fullerenol; D005682:Gadolinium
keywords: Adoptive immunotherapy; Cancer; Fullerenol; Macrophage