March 6, 2006
Boron Neutron Capture Using Boron Nanoparticles
Boron neutron capture therapy, an experimental therapy for treating brain cancer, could get a boost thanks to the development of boron carbide nanoparticles that can be targeted for uptake by cancer cells. Such nanoparticles could provide a much needed method for increasing the amount of boron that gets into tumor cells rather than remaining in circulation.
First developed in the 1950s and 1960s, boron neutron capture therapy involves first administering a boron-containing compound and then irradiating tumors, in which the boron compound has presumably become concentrated, with high energy neutron from a small nuclear reactor. Boron atoms absorb neutrons efficiently and then release alpha particles, which then kill cells containing boron. Clinical trials of boron neutron capture therapy have been disappointing, in large part because of the difficulty in getting enough boron into tumor cells and in clearing from the body any boron not taken up by tumors.
The new boron carbide nanoparticles developed by Thomas Bjørnholm, Ph.D., and colleagues at the University of Copenhagen, in Denmark, may be able to solve this problem. Writing in the journal Applied Radiation and Isotopes, the Danish researchers describe how they prepared 73-nanometer-diameter boron carbide nanoparticles for uptake by T cells that are targeted to tumors. These T cells can be isolated from a patient, loaded with the nanoparticles, and then reintroduced into the patient, where in theory, they travel to tumors and deliver the nanoparticles.
In a second paper, published in the journal Bioconjugate Chemistry, the investigators then described the surface modification techniques they developed in order to coat the boron carbide nanoparticles with a peptide that improves cell uptake, and a fluorescent dye for tracking the movement of the particles through the body. Experiments with the modified nanoparticles showed that both melanoma and thymoma cells (the cells that produce T cells) took up large amounts of these nanoparticles. Subsequent experiments showed that neutron irradiation successfully killed cells that had taken up the boron nanoparticles.
This work, which also involved researchers from the University of Aarhus, in Denmark, and T-Cellic A/S, in Hørsholm, Denmark, is detailed in two papers. The first, covering the preparation of boron carbide nanoparticles, appears in a paper titled, “Preparation and characterization of Boron carbide nanoparticles for use as a novel agent in T cell-guided boron neutron capture therapy.” An abstract of this paper is available through PubMed.
The second paper, detailing the functionalization and cellular uptake of these nanoparticles, is titled, “Functionalization and cellular uptake of boron carbide nanoparticles. The first step toward T cell-guided boron neutron capture therapy.” This paper was published online in advance of print publication. An abstract is available through the journal’s website.