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Ablation of Breast Cancer Cells Using Trastuzumab‐Functionalized Multi‐Walled Carbon Nanotubes and Trastuzumab‐Diphtheria Toxin Conjugate
Author(s) -
Oraki Kohshour Mojtaba,
Mirzaie Sako,
Zeinali Majid,
Amin Mansour,
Said Hakhamaneshi Mohammad,
Jalili Ali,
Mosaveri Nader,
Jamalan Mostafa
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12244
Subject(s) - trastuzumab , diphtheria toxin , cancer cell , immunoconjugate , conjugate , immunotoxin , cytotoxicity , cancer research , monoclonal antibody , chemistry , breast cancer , cancer , antibody , medicine , biochemistry , toxin , in vitro , immunology , mathematical analysis , mathematics
Trastuzumab ( H erceptin ® ) is a monoclonal antibody (m Ab ) for specific ablation of HER 2‐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 MWCNT s. Then, antiproliferative activity of the fusion constructs against HER 2‐overexpressing SK ‐ BR ‐3 and also HER 2‐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 MWCNT s 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 MWCNT s 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 HER 2‐overexpressing cancerous cells.