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  3. Orchestrating apoptosis and ferroptosis through enhanced sonodynamic therapy using amorphous UIO-66-CoOx

Orchestrating apoptosis and ferroptosis through enhanced sonodynamic therapy using amorphous UIO-66-CoOx

  • J Colloid Interface Sci. 2024 Aug:667:91-100. doi: 10.1016/j.jcis.2024.04.064.
Xiuxin Lu 1,  Yang Zheng 2,  Yan Liu 3,  Dan Li 1,  Jiaxin Lin 1,  Lineng Wei 1,  Song Gao 4,  Junjie Liu 5,  Weiqing Zhang 6,  Yanbo Chen 7
Affiliations

Affiliations

  • 1 Department of Research, Department of Ultrasonography, Guangxi Medical University Cancer Hospital, Guangxi Medical University, Nanning, Guangxi 530021, China.
  • 2 Department of Plastic Surgery, The Second Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi 530021, China.
  • 3 Department of Breast, Bone and Soft Tissue Oncology, Guangxi Medical University Cancer Hospital, Nanning, Nanning 530021, China; Laboratory of Breast Cancer Diagnosis and Treatment Research of Guangxi Department of Education, Guangxi Medical University Cancer Hospital, Nanning 530021, China.
  • 4 Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin 150081, China.
  • 5 Department of Research, Department of Ultrasonography, Guangxi Medical University Cancer Hospital, Guangxi Medical University, Nanning, Guangxi 530021, China. Electronic address: liujunjie197806@163.com.
  • 6 Department of Research, Department of Ultrasonography, Guangxi Medical University Cancer Hospital, Guangxi Medical University, Nanning, Guangxi 530021, China. Electronic address: zhangweiqing@tjut.edu.cn.
  • 7 Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin 150081, China. Electronic address: hmucyb@163.com.
PMID: 38621335 DOI: 10.1016/j.jcis.2024.04.064
Abstract

The development of efficient and multifunctional sonosensitizers is crucial for enhancing the efficacy of sonodynamic therapy (SDT). Herein, we have successfully constructed a CoOx-loaded amorphous metal-organic framework (MOF) UIO-66 (A-UIO-66-CoOx) sonosensitizer with excellent catalase (CAT)- and glutathione-oxidase (GSH-OXD)-like activities. The A-UIO-66-CoOx exhibits a 2.6-fold increase in singlet oxygen (1O2) generation under ultrasound (US) exposure compared to crystalline UIO-66 sonosensitizer, which is attributed to its superior charge transfer efficiency and consistent oxygen (O2) supply. Additionally, the A-UIO-66-CoOx composite reduces the expression of Glutathione Peroxidase (GPX4) by depleting glutathione (GSH) through Co3+ and Co2+ valence changes. The high levels of highly cytotoxic 1O2 and deactivation of GPX4 can lead to lethal lipid peroxidation, resulting in concurrent Apoptosis and Ferroptosis. Both in vitro and vivo tumor models comprehensively confirmed the enhanced SDT antitumor effect using A-UIO-66-CoOx sonosensitizer. Overall, this study emphasizes the possibility of utilizing amorphization engineering to improve the effectiveness of MOFs-based sonosensitizers for combined Cancer therapies.

Keywords

Antitumor; Apoptosis; Ferroptosis; Metal-organic framework; Sonodynamic therapy.

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