Photodynamic therapy (PDT) works well and has few side effects, but is traditionally ineffective for deeply embedded or metastatic tumors. A new approach targets previously inaccessible tissues by leveraging materials already approved for cancer treatment. Instead of applying light externally, researchers at Washington University School of Medicine in St. Louis (WUSTL; Missouri) delivered light—and a photosensitive source of free radicals that can be activated by light-directly to tumor cells.1
Samuel Achilefu, Ph.D., professor of radiology and of biomedical engineering, and Nalinikanth Kotagiri, MD, Ph.D., a postdoctoral researcher, focused on a widely used imaging strategy called FDG-PET. With this technique, patients receive an intravenous dose of radiolabeled sugar molecules called fluorodeoxyglucose (FDG). Many tumors take up the sugar, and the attached radioactive fluorine makes them light up on a PET scan. The researchers hypothesized that the fluorine would produce enough Cerenkov radiation to activate a photosensitizing agent if it could also be delivered to the same location. In this way, FDG could serve as an imaging agent and also provide light for phototherapy.
|A photosensitive titanium dioxide nanoparticle (purple) carries the iron-binding protein transferrin (blue and green) and the light-sensitive cancer drug titanocene (red) to a deeply embedded tumor, where it can be activated using fluorodeoxyglucose (FDG), a radiolabeled agent used in PET scanning.|
For photosensitization, they chose titanium dioxide nanoparticles, which, when exposed to light, produces free radicals without requiring oxygen for the reaction. To increase the particles' potency, they added titanocene—a drug approved for investigational use in humans—to their surface, and then a coating of a protein called transferrin that binds to iron in the blood (many tumors rely on iron to grow).
They tested different formulations of the nanoparticles and cancer drug combined with the FDG light source in mice with human tumors. When injected into the bloodstream with FDG, the nanoparticles that carried the drug had the most significant effect. Fifteen days after treatment, tumors in treated mice were eight times smaller than those in untreated mice.
Exposed to light, the titanium dioxide alone can kill cancer, Achilefu says. "But adding the drug appears to enhance the therapeutic outcome. The two together produce different kinds of free radicals that overwhelm tumor cells. Our formulation also uses doses of the drug that are much lower than would be administered for chemotherapy." Side effects should be minimal; the researchers are planning a small clinical trial in humans.
1. N. Kotagiri, G. P. Sudlow, W. J. Akers, and S. Achilefu, NatureNanotechnol., doi:10.1038/nnano.2015.17 (2015).