Citation: Guanghui Lin, Jieyao Chen, Xiaojia Liu, Yitong Lin, Xudong Zhu, Guotao Yuan, Bowen Yang, Shuanshuan Guo, Yue Pan, Jianhua Zhou. Sustained modulation of tumor microenvironment via sorafenib-loaded mesoporous ferromanganese nanozymes for enhanced apoptosis-ferroptosis cancer therapy[J]. Chinese Chemical Letters, ;2025, 36(8): 111018. doi: 10.1016/j.cclet.2025.111018 shu

Sustained modulation of tumor microenvironment via sorafenib-loaded mesoporous ferromanganese nanozymes for enhanced apoptosis-ferroptosis cancer therapy

Guanghui Lin ^{a, 1} ,
Jieyao Chen ^{b, 1} ,
Xiaojia Liu ^{b, 1} ,
Yitong Lin ^b ,
Xudong Zhu ^b ,
Guotao Yuan ^b ,
Bowen Yang ^b ,
Shuanshuan Guo ^a ,
Yue Pan ^{b, *,} ,
Jianhua Zhou ^{a, *,}

a.
School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China
b.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China

panyue@mail.sysu.edu.cn

zhoujh33@mail.sysu.edu.cn

Received Date: 28 November 2024
Revised Date: 26 February 2025
Accepted Date: 27 February 2025
Available Online: 27 February 2025

Figures(5)

Sorafenib (Sora) not only has an inhibitory effect on angiogenesis via indirectly inhibiting tumor growth through antiangiogenesis, but also can inactivate the glutathione peroxidase 4 (GPX4) to induce ferroptosis. Nonetheless, the therapeutic efficacy is hampered by a plethora of factors, including low bioavailability and tumor microenvironment (TME). Of particular note is the hypoxic and reductive TME, which acts as a significant impediment and poses formidable challenges to attain the most optimal treatment outcomes. Herein, we developed a novel therapeutic platform based on Sora-loaded mesoporous ferromanganese nanoparticles (PMFNs@Sora). PMFNs mimics both catalase and GPX activities. The self-sustained catalase activity enables continuous decomposition of hydrogen peroxide to generate oxygen, which alleviates hypoxia microenvironment. The GPX activity simultaneously amplifies the therapeutic efficacy of Sora. The as-synthesized PMFNs@Sora demonstrates significantly enhanced antitumor effect in vitro through apoptosis-ferroptosis, revealed by Western blot. Furthermore, PMFNs@Sora also showed effective tumor growth inhibition in vivo. This multifunctional nanoplatform offers a promising strategy for modulating the TME and enhancing cancer treatment in clinical application.
- Ferromanganese,
- Nanozyme,
- Sorafenib,
- Ferroptosis,
- Tumor microenvironment
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