Abstract
Auger electron therapy and photodynamic therapy (PDT) have attracted attention as powerful anticancer modalities. Herein, we report the development of novel bimodal agents for Auger electron therapy and PDT, and their application to combination therapy. [125I]NBH-1/NBH-1 and [125I]NBH-2/NBH-2, composing Hoechst and iodostyryl-BODIPY, were synthesized and evaluated regarding their usefulness as bimodal agents. [125I]NBH-1 showed significantly higher nuclear uptake than [125I]NBH-2 and radioactivity-dependent cytotoxicity induced by Auger electrons. In addition, NBH-1 exhibited photoinduced cytotoxicity. Combination therapy using [125I]NBH-1 and NBH-1 with light irradiation induced a superior cytotoxicity to these treatments alone. In tumor-bearing mice injected with NBH-1 or [125I]NBH-1/NBH-1 under light irradiation, significant tumor growth inhibition was observed compared with that of the control group. Especially, [125I]NBH-1/NBH-1 under light irradiation showed the strongest therapeutic effects among all treatments. These results suggest that [125I]NBH-1/NBH-1 is a potent bimodal agent for Auger therapy and PDT and that combination therapy using [125I]NBH-1 and NBH-1 shows enhanced therapeutic efficacy.
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