title: The Architecture and Function of Monoclonal Antibody-Functionalized Mesoporous Silica Nanoparticles Loaded with Mifepristone: Repurposing Abortifacient for Cancer Metastatic Chemoprevention.
abstract: The circulating tumor cells (CTCs) existing in cancer survivors are considered the root cause of cancer metastasis. To prevent the devastating metastasis cascade from initiation, we hypothesize that a biodegradable nanomaterial loaded with the abortifacient mifepristone (MIF) and conjugated with the epithelial cell adhesion molecule antibody (aEpCAM) may serve as a safe and effective cancer metastatic preventive agent by targeting CTCs and preventing their adhesion-invasion to vascular intima. It is demonstrated that MIF-loaded mesoporous silica nanoparticles (MSN) coated with aEpCAM (aE-MSN-M) can specifically target and bind colorectal cancer cells in either cell medium or blood through EpCAM recognition proven by quantitative flow cytometric detection and free aEpCAM competitive assay. The specific binding results in downregulation of the captured cells and drives them into G0/G1 phase primarily attributed to the effect of aEpCAM. The functional nanoparticles significantly inhibit the heteroadhesion between cancer cells and endothelial cells, suggesting the combined inhibition effects of aEpCAM and MIF on E-selectin and ICAM-1 expression. The functionalized nanoparticles circulate in mouse blood long enough to deliver MIF and inhibit lung metastasis. The present proof-of-concept study shows that the aE-MSN-M can prevent cancer metastasis by restraining CTC activity and their adhesion-invasion to vascular intima.
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Songen
authors.initials: S
authors.lastname: Gu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xie
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Yewei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Wenge
authors.initials: W
authors.lastname: Chen
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Dong
authors.affiliation: Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ, 08854-8020, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Sinko
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Lee
authors.initials: L
authors.lastname: Jia
mesh_terms: D000021:Abortifacient Agents, Steroidal / Q000008:administration & dosage / Q000737:chemistry; D065966:Absorption, Physicochemical; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary*; D004058:Diffusion; D016503:Drug Delivery Systems / Q000379:methods; D058492:Drug Repositioning; D000071858:Epithelial Cell Adhesion Molecule / Q000276:immunology*; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D015735:Mifepristone / Q000008:administration & dosage* / Q000737:chemistry; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D058726:Nanoconjugates / Q000008:administration & dosage / Q000737:chemistry; D058608:Nanopores / Q000648:ultrastructure; D012822:Silicon Dioxide / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D000021:Abortifacient Agents, Steroidal; D000911:Antibodies, Monoclonal; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D053769:Nanocapsules; D058726:Nanoconjugates; D015735:Mifepristone; D012822:Silicon Dioxide
keywords: EpCAM; circulating tumor cells; mesoporous silica nanoparticles; mifepristone, cancer