The overall objective of this SBIR proposal is to develop new anticancer agents which are cytotoxic in photodynamic therapy (PDT). It has been shown by Morgan and Boyer that pyrromethene boron difluoride (P-BF2) complexes can offer this property. In Phase I, substituted (P-BF2) complexes will be prepared, characterized and evaluated for PDT potentials. Studies have documented that human ovarian cancer cells (LS-2) cultured with the disodium salt of pentamethylpyrromethene-2, 6-disulfonate boron difluoride (PMPDS-BF2) plus exposure to light produced cell growth inhibition. In addition, when PMPDS-BF2 was injected intratumor into the DMBA-rat breast cancer model, followed by exposure to quartz lamp irradiation, 50-100% tumor remissions occurred. Cyano, bistetramethylene and acetoxymethyl substituted P-BF2 complexes will be evaluated in vitro and in vivo in mouse and rat tumor models. The P-BF complexes are considered to be quasiaromatic electron impoverished (QA-eI) heterocycles. They show high extinction coefficients, high fluorescent quantum yields: those with superior laser action poses little to no triplet-triplet absorption in the fluorescence spectral region. These properties will be considered and attempts to associate them to PDT will be made.
| Larson, R A; Daley, G Q; Schiffer, C A et al. (2003) Treatment by design in leukemia, a meeting report, Philadelphia, Pennsylvania, December 2002. Leukemia 17:2358-82 |
