Jun 24, 2008
Nanotubes turn up the heat on cancer
The ability of carbon nanotubes to convert near-infrared (NIR) light into heat offers a promising means for thermal ablation of cancer cells. Hyperthermia has been used clinically in the management of solid tumours as it can boost the cytotoxic effects of chemotherapy or radiotherapy, as well as preferentially increase the permeability of tumour vasculature to enhance drug delivery. Now, researchers have demonstrated the use of monoclonal antibodies to target such nanotubes directly to cancer cells.
Monoclonal antibodies target molecules on the surface of cancer cells - in this case, specific sites on lymphoma cells. The research team - from UT Southwestern Medical Center (Dallas, TX), Massachusetts Institute of Technology (Cambridge, MA) and the University of Texas at Dallas (Richardson, TX) - coated carbon nanotubes with the monoclonal antibodies and examined their in vitro effect on cultures of cancerous lymphoma cells.
The antibody-coated nanotubes showed specific binding to the tumour cells' surfaces. When these cells were then exposed to NIR laser light (805 to 811 nm), the nanotubes heated up and generated enough heat to kill the cells. The use of NIR light (in the 700 to 1100 nm range) to induce hyperthermia is particularly attractive because tissue does not strongly absorb in this range. Thus the light should effectively and safely penetrate normal tissue and ablate any tumour cells to which the nanotubes are attached.
Importantly, only the specifically targeted cells were killed after NIR light exposure. The team also demonstrated that nanotubes coated with an unrelated antibody neither bound to nor killed the tumour cells. "Demonstrating this specific killing was the objective of this study," said Ellen Vitetta, director of the Cancer Immunobiology Center at UT Southwestern and senior author of the PNAS paper.
The use of carbon nanotubes to destroy cancer cells with heat is being explored by several research groups, but this study is the first to show that both the antibody and the carbon nanotubes retained their physical properties and their functional abilities - binding to and killing only the targeted cells. This was true even when the antibody-nanotube complex was placed in a setting designed to mimic conditions inside the human body.
The next step in this work is the evaluation of the pharmacokinetics, biodistribution, toxicity and activity of the antibody-nanotube constructs in vivo. "We have worked with targeted therapies for many years, and even when this degree of specificity can be demonstrated in a laboratory dish, there are many hurdles to translating these new therapies into clinical studies," Vitetta explained. "We're just beginning to test this in mice, and although there is no guarantee it will work, we are optimistic."
The researchers presented their work in PNAS.