title: Targeting Colorectal Cancer Stem-Like Cells with Anti-CD133 Antibody-Conjugated SN-38 Nanoparticles.
abstract: Cancer stem-like cells play a key role in tumor development, and these cells are relevant to the failure of conventional chemotherapy. To achieve favorable therapy for colorectal cancer, PEG-PCL-based nanoparticles, which possess good biological compatibility, were fabricated as nanocarriers for the topoisomerase inhibitor, SN-38. For cancer stem cell therapy, CD133 (prominin-1) is a theoretical cancer stem-like cell (CSLC) marker for colorectal cancer and is a proposed therapeutic target. Cells with CD133 overexpression have demonstrated enhanced tumor-initiating ability and tumor relapse probability. To resolve the problem of chemotherapy failure, SN-38-loaded nanoparticles were conjugated with anti-CD133 antibody to target CD133-positive (CD133(+)) cells. In this study, anti-CD133 antibody-conjugated SN-38-loaded nanoparticles (CD133Ab-NPs-SN-38) efficiently bound to HCT116 cells, which overexpress CD133 glycoprotein. The cytotoxic effect of CD133Ab-NPs-SN-38 was greater than that of nontargeted nanoparticles (NPs-SN-38) in HCT116 cells. Furthermore, CD133Ab-NPs-SN-38 could target CD133(+) cells and inhibit colony formation compared with NPs-SN-38. In vivo studies in an HCT116 xenograft model revealed that CD133Ab-NPs-SN-38 suppressed tumor growth and retarded recurrence. A reduction in CD133 expression in HCT116 cells treated with CD133Ab-NPs-SN-38 was also observed in immunohistochemistry results. Therefore, this CD133-targeting nanoparticle delivery system could eliminate CD133-positive cells and is a potential cancer stem cell targeted therapy.
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University , Taipei 100, Taiwan.
authors.forename: Sin-Tzu
authors.initials: ST
authors.lastname: Ning
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University , Taipei 100, Taiwan.
authors.forename: Shin-Yu
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University , Taipei 100, Taiwan.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Wei
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research , Longtan, Taoyuan 325, Taiwan.
authors.forename: Cheng-Liang
authors.initials: CL
authors.lastname: Peng
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University , Taipei 100, Taiwan.
authors.forename: Susan Yun-Fan
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University , Taipei 100, Taiwan.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University , Taipei 100, Taiwan.
authors.forename: Pei-Chi
authors.initials: PC
authors.lastname: Lee
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University , Taipei 100, Taiwan.|Isotope Application Division, Institute of Nuclear Energy Research , Longtan, Taoyuan 325, Taiwan.
authors.forename: Ying-Hsia
authors.initials: YH
authors.lastname: Shih
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University , Taipei 100, Taiwan.
authors.forename: Chun-Yen
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research , Longtan, Taoyuan 325, Taiwan.
authors.forename: Tsai-Yueh
authors.initials: TY
authors.lastname: Luo
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University , Taipei 100, Taiwan.|Department of Oncology, National Taiwan University Hospital and College of Medicine , Taipei 100, Taiwan.
authors.forename: Ming-Jium
authors.initials: MJ
authors.lastname: Shieh
mesh_terms: D000071916:AC133 Antigen / Q000096:biosynthesis / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D000077146:Irinotecan; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; C000606023:PROM1 protein, human; D000077146:Irinotecan; D002166:Camptothecin
keywords: CD133; SN-38; cancer stem-like cells; colorectal cancer; nanoparticles