Ablation of Breast Cancer Cells Using Trastuzumab‐Functionalized Multi‐Walled Carbon Nanotubes and Trastuzumab‐Diphtheria Toxin Conjugate

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.