Li Jia, Hu Zheng, Zhu Jiwei, Lin Xin, Gao Xu, Lv Guixiang
Department of Biochemistry and Molecular Biology, Harbin Medical University, Basic Medical Institute of Heilongjiang Medical Sciences Academy, Harbin 150086, China.
School of Medicine and Health, Harbin Institute of Technology, Harbin 150080, China.
Pharmaceutics. 2023 Sep 4;15(9):2275. doi: 10.3390/pharmaceutics15092275.
Sonodynamic therapy (SDT) induces reactive oxygen species (ROS) to kill tumor cells. Heme oxygenase-1 (HO-1), as an important antioxidant enzyme, resists killing by scavenging ROS. Zinc protoporphyrin (ZnPP) not only effectively inhibits HO-1 activity, but also becomes a potential sonosensitizer. However, its poor water solubility limits its applications. Herein, we developed an improved water-soluble method. It was proved that pegylated zinc protoporphyrin-mediated SDT (PEG-ZnPP-SDT) could significantly enhance ROS production by destroying the HO-1 antioxidant system in ovarian cancer. Increased ROS could cause mitochondrial membrane potential collapse, release cytochrome c from mitochondria to the cytoplasm, and trigger the mitochondrial-caspase apoptotic pathway. In conclusion, our results demonstrated that PEG-ZnPP-SDT, as a novel sonosensitizer, could improve the antitumor effects by destroying the HO-1 antioxidant system. It provided a new therapeutic strategy for SDT to treat cancers, especially those with higher HO-1 expression.
声动力疗法（SDT）可诱导活性氧（ROS）生成以杀死肿瘤细胞。血红素加氧酶-1（HO-1）作为一种重要的抗氧化酶，通过清除ROS来抵抗杀伤。锌原卟啉（ZnPP）不仅能有效抑制HO-1活性，还成为一种潜在的声敏剂。然而，其水溶性差限制了其应用。在此，我们开发了一种改进的水溶性方法。结果证明，聚乙二醇化锌原卟啉介导的声动力疗法（PEG-ZnPP-SDT）可通过破坏卵巢癌中的HO-1抗氧化系统显著增强ROS生成。增加的ROS可导致线粒体膜电位崩溃，使细胞色素c从线粒体释放到细胞质中，并触发线粒体-半胱天冬酶凋亡途径。总之，我们的结果表明，PEG-ZnPP-SDT作为一种新型声敏剂，可通过破坏HO-1抗氧化系统提高抗肿瘤效果。它为声动力疗法治疗癌症，尤其是HO-1表达较高的癌症提供了一种新的治疗策略。
