Repository of Research and Investigative Information

Repository of Research and Investigative Information

Kurdistan University of Medical Sciences

Ablation of breast cancer cells using trastuzumab-functionalized multi-walled carbon nanotubes and trastuzumab-diphtheria toxin conjugate

(2014) Ablation of breast cancer cells using trastuzumab-functionalized multi-walled carbon nanotubes and trastuzumab-diphtheria toxin conjugate. Chemical Biology and Drug Design.

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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. © 2013 John Wiley & Sons A/S.

Item Type: Article
Keywords: diphtheria toxin; diphtheria toxin conjugate; multi walled nanotube; trastuzumab; unclassified drug, absorption; antiproliferative activity; article; breast cancer cell; cancer cell; cell proliferation; cell strain MCF 7; cytotoxicity; heat; human; human cell; priority journal; radiation, HER2 receptor; multiwalled carbon nanotubes; nano-immunoconjugate; thermal ablation; trastuzumab, Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Diphtheria Toxin; Drug Carriers; Female; Humans; Infrared Rays; MCF-7 Cells; Nanotubes, Carbon; Temperature
Page Range: pp. 259-265
Journal or Publication Title: Chemical Biology and Drug Design
Volume: 83
Number: 3
Publisher: Blackwell Publishing Ltd
Identification Number: 10.1111/cbdd.12244
ISSN: 17470277
Depositing User: مهندس جمال محمودپور

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