Versatile Nanodrugs Containing Glutathione and Heme Oxygenase 1 Inhibitors Enable Suppression of Antioxidant Defense System in a Two‐Pronged Manner for Enhanced Photodynamic Therapy. Issue 19 (30th June 2021)

• Record Type: Journal Article
• Authors: Zhong, Hao; Huang, Pei‐Ying; Yan, Ping; Chen, Pei‐Ling; Shi, Qun‐Yin; Zhao, Ze‐An; Chen, Jing‐Xuan; Shu, Xian; Wang, Ping; Yang, Bin; Zhou, Zheng‐Zheng; Chen, Jian‐Jun; Pang, Jian‐Xin; Tu, Ying‐Feng; Liu, Li‐Han; Zhang, Xian‐Zheng
• Is Part Of: Advanced healthcare materials. Volume 10:Issue 19(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-06-30
• Subjects: antioxidant defense suppression -- carrier‐free nanomedicine -- GSH depletion -- photodynamic therapy -- self‐assembly; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.202100770
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: The antioxidant defense system in malignant cells, which involves antioxidant enzymes and antioxidant molecules, is an innate barrier to photodynamic therapy (PDT). Because of the complexity of the endogenous antioxidant mechanisms of these cells, simply inhibiting individual antioxidant pathways has a limited effect on improving the lethality of ROS. To enhance the efficacy of PDT for tumor treatment, a versatile nanoparticle (NP)‐based drug is developed, which the authors call PZB NP, containing the glutathione inhibitor l ‐buthionine sulfoximine (BSO) and the heme oxygenase 1 (HO‐1) inhibitor protoporphyrin zinc(II) (ZnPP) to suppress the innate antioxidant defense system of cancer cells in a two‐pronged manner. BSO reduces intracellular glutathione levels to minimize ROS elimination and protein protection during PDT, and ZnPP inhibits the ROS‐stimulated upregulation of the antioxidant HO‐1, thus preventing ROS removal by cells after PDT. Thus, BSO and ZnPP synergistically suppress the antioxidant defense systems of cancer cells both during and after protoporphyrin‐IX‐mediated PDT in a two‐pronged manner, resulting in tumor cell death through excess oxidative pressure. The results demonstrate that the construction of nanodrugs having dual antioxidation defense suppression properties is a promising route for the development of highly efficient ROS‐based therapies. Abstract : A simple and versatile nanodrug, PZB nanoparticle, is developed to enhance PDT efficacy using a two‐pronged antioxidant suppression strategy. In short, the nanoparticle‐loaded BSO reduces the existing intracellular antioxidant (glutathione) concentration before PDT. Subsequently, the loaded protoporphyrin zinc(II) (ZnPP) inhibits ROS‐stimulated antioxidant enzymes (heme oxygenase 1) after PDT. These significantly enhance intracellular oxidative stress, leading to increased cancer cell death.