Synthesis and biological evaluation of bi-modal BODIPY-conjugated Hoechst applicable for Auger-electron and photodynamic cancer therapy.

Current therapeutic approaches to cancer are not fully effective, and so development of more effective treatment is needed. Auger-electron therapy and photodynamic therapy have attracted marked attentions as a promising strategy in cancer treatment. In this study, we synthesized [I]BH-2/BH-2, which comprised Hoechst and 2,6-diiodo-substituted BODIPY, and evaluated its usefulness as a bi-modal agent for Auger-electron/photodynamic therapy by comparison with the previously reported compound [I]BH/BH. [I]BH-2 was obtained at a 13% radiochemical yield. [I]BH-2 showed similar uptake into the nucleus to [I]BH, suggesting that Hoechst can function as a nuclear localization tag. HeLa cell viabilities were reduced in both cells exposed to [I]BH-2 and [I]BH. γ-H2AX foci in HeLa cells exposed to [I]BH-2 or [I]BH were increased in a dose-dependent manner, indicating that DNA double-strand breaks may have occurred. No significant difference was observed between [I]BH-2 and [I]BH at these investigations. For PDT application, BH-2 showed a higher singlet oxygen quantum yield (Φ) and caused superior photo-induced cytotoxicity in HeLa cells compared with BH. These results suggest that bi-modal [I]BH-2/BH-2 can cause anti-tumor effects with Auger-electron and photodynamic therapy.