Onoue Ryotaro, Watanabe Hiroyuki, Ono Masahiro
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
ACS Pharmacol Transl Sci. 2024 Apr 29;7(5):1395-1403. doi: 10.1021/acsptsci.4c00035. eCollection 2024 May 10.
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. [I]NBH-1/NBH-1 and [I]NBH-2/NBH-2, composing Hoechst and iodostyryl-BODIPY, were synthesized and evaluated regarding their usefulness as bimodal agents. [I]NBH-1 showed significantly higher nuclear uptake than [I]NBH-2 and radioactivity-dependent cytotoxicity induced by Auger electrons. In addition, NBH-1 exhibited photoinduced cytotoxicity. Combination therapy using [I]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 [I]NBH-1/NBH-1 under light irradiation, significant tumor growth inhibition was observed compared with that of the control group. Especially, [I]NBH-1/NBH-1 under light irradiation showed the strongest therapeutic effects among all treatments. These results suggest that [I]NBH-1/NBH-1 is a potent bimodal agent for Auger therapy and PDT and that combination therapy using [I]NBH-1 and NBH-1 shows enhanced therapeutic efficacy.
俄歇电子疗法和光动力疗法（PDT）作为强大的抗癌方式已引起关注。在此，我们报告了用于俄歇电子疗法和PDT的新型双模态剂的开发及其在联合治疗中的应用。合成了由Hoechst和碘代苯乙烯基 - BODIPY组成的[I]NBH - 1/NBH - 1和[I]NBH - 2/NBH - 2，并评估了它们作为双模态剂的效用。[I]NBH - 1显示出比[I]NBH - 2显著更高的核摄取以及由俄歇电子诱导的放射性依赖性细胞毒性。此外，NBH - 1表现出光诱导的细胞毒性。使用[I]NBH - 1和NBH - 1并结合光照射的联合治疗诱导出比单独这些治疗更高的细胞毒性。在光照下注射了NBH - 1或[I]NBH - 1/NBH - 1的荷瘤小鼠中，与对照组相比观察到显著的肿瘤生长抑制。特别是，光照下的[I]NBH - 1/NBH - 1在所有治疗中显示出最强的治疗效果。这些结果表明，[I]NBH - 1/NBH - 1是用于俄歇疗法和PDT的有效双模态剂，并且使用[I]NBH - 1和NBH - 1的联合治疗显示出增强的治疗效果。
