Antitumor Effects of Pegylated Zinc Protoporphyrin-Mediated Sonodynamic Therapy in Ovarian Cancer.

Pharmaceutics

Department of Biochemistry and Molecular Biology, Harbin Medical University, Basic Medical Institute of Heilongjiang Medical Sciences Academy, Harbin 150086, China.

Published: September 2023

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10534787PMC
http://dx.doi.org/10.3390/pharmaceutics15092275DOI Listing

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