title: Ablation of breast cancer cells using trastuzumab-functionalized multi-walled carbon nanotubes and trastuzumab-diphtheria toxin conjugate.
abstract: Trastuzumab (Herceptin(®) ) is a monoclonal antibody (mAb) for specific ablation of HER2-overexpressing malignant breast cancer cells. Intensification of antiproliferative activity of trastuzumab through construction of immunotoxins and nano-immunoconjugates is a promising approach for treatment of cancer. In this study, trastuzumab was directly conjugated to diphtheria toxin (DT). Also, conjugates of trastuzumab and multiwalled carbon nanotubes (MWCNT) were constructed by covalent immobilization of trastuzumab onto MWCNTs. Then, antiproliferative activity of the fusion constructs against HER2-overexpressing SK-BR-3 and also HER2-negative MCF-7 cancer cell lines were examined. Cells treated with trastuzumab-MWCNT conjugates were irradiated with near-infrared (NIR) light. Efficient absorption of NIR radiation and its conversion to heat by MWCNTs can be resulted to thermal ablation of cancerous cells. Our results strongly showed that both trastuzumab-MWCNT and trastuzumab-DT conjugates were significantly efficient in the specific killing of SK-BR-3 cells. Targeting of MWCNTs to cancerous cells using trastuzumab followed by exposure of cells to NIR radiation was more efficient in repression of cell proliferation than treatment for cancer cells with trastuzumab-DT. Our results also showed that conjugation linkers can significantly affect the cytotoxicity of MWCNT-immunoconjugates. In conclusion, our data demonstrated that trastuzumab-MWCNT is a promising nano-immunoconjugate for killing of HER2-overexpressing cancerous cells.
authors.affiliation: Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Golestan Avenue, Ahvaz 15794-61357, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Oraki Kohshour
authors.forename: Sako
authors.initials: S
authors.lastname: Mirzaie
authors.forename: Majid
authors.initials: M
authors.lastname: Zeinali
authors.forename: Mansour
authors.initials: M
authors.lastname: Amin
authors.forename: Mohammad
authors.initials: M
authors.lastname: Said Hakhamaneshi
authors.forename: Ali
authors.initials: A
authors.lastname: Jalili
authors.forename: Nader
authors.initials: N
authors.lastname: Mosaveri
authors.forename: Mostafa
authors.initials: M
authors.lastname: Jamalan
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004167:Diphtheria Toxin / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D006801:Humans; D007259:Infrared Rays; D061986:MCF-7 Cells; D037742:Nanotubes, Carbon / Q000737:chemistry*; D013696:Temperature; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D004337:Drug Carriers; D037742:Nanotubes, Carbon; D000068878:Trastuzumab
keywords: HER2 receptor; multiwalled carbon nanotubes; nano-immunoconjugate; thermal ablation; trastuzumab