The importance of cellular internalization of antibody-targeted carbon nanotubes in the photothermal ablation of breast cancer cells.
Single-walled carbon nanotubes (CNTs) convert absorbed near infrared (NIR) light into heat. The use of CNTs in the NIR-mediated photothermal ablation of tumor cells is attractive because the penetration of NIR light through normal tissues is optimal and the side effects are minimal. Targeted thermal ablation with minimal collateral damage can be achieved by using CNTs attached to tumor-specific monoclonal antibodies (MAbs). However, the role that the cellular internalization of CNTs plays in the subsequent sensitivity of the target cells to NIR-mediated photothermal ablation remains undefined. To address this issue, we used CNTs covalently coupled to an anti-Her2 or a control MAb and tested their ability to bind, internalize, and photothermally ablate Her2(+) but not Her2(-) breast cancer cell lines. Using flow cytometry, immunofluorescence, and confocal Raman microscopy, we observed the gradual time-dependent receptor-mediated endocytosis of anti-Her2-CNTs whereas a control MAb-CNT conjugate did not bind to the cells. Most importantly, the Her2(+) cells that internalized the MAb-CNTs were more sensitive to NIR-mediated photothermal damage than cells that could bind to, but not internalize the MAb-CNTs. These results suggest that both the targeting and internalization of MAb-CNTs might result in the most effective thermal ablation of tumor cells following their exposure to NIR light.
Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Radu
R
Marches
Carole
C
Mikoryak
Ru-Hung
RH
Wang
Paul
P
Pantano
Rockford K
RK
Draper
Ellen S
ES
Vitetta
D000906:Antibodies / Q000737:chemistry*; D000912:Antibodies, Neoplasm / Q000737:chemistry*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000628:therapy*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007259:Infrared Rays / Q000627:therapeutic use; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000528:radiation effects*; D010789:Phototherapy / Q000379:methods*
D000906:Antibodies; D000912:Antibodies, Neoplasm; D037742:Nanotubes, Carbon