Ablation of Breast Cancer Cells Using Trastuzumab‐Functionalized Multi‐Walled Carbon Nanotubes and Trastuzumab‐Diphtheria Toxin Conjugate |
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Authors: | Mojtaba Oraki Kohshour Sako Mirzaie Majid Zeinali Mansour Amin Mohammad Said Hakhamaneshi Ali Jalili Nader Mosaveri Mostafa Jamalan |
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Institution: | 1. Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, , Golestan Avenue, Ahvaz 15794‐61357, Iran;2. Department of Biochemistry, Islamic Azad University, , Pasdaran Avenue, Sanandaj 618, Iran;3. Biotechnology Research Center, Research Institute of Petroleum Industry (RIPI), , West Blvd. Azadi Sports Complex, Tehran 14665‐137, Iran;4. Department of Microbiology, School of Medicine, Infectious and Tropical Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, , Golestan Avenue, Ahvaz 618, Iran;5. Faculty of Medicine, Kurdistan Cellular & Molecular Research Center, Kurdistan University of Medical Science, , Abidar Avenue, Sanandaj 6618634683, Iran;6. Razi Vaccine and Serum Research Institute, , Hessarak, Karaj 31975/148, Iran |
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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. |
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Keywords: | HER2 receptor multiwalled carbon nanotubes nano‐immunoconjugate thermal ablation trastuzumab |
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