Hydrogen (H2) therapy has been widely studied in the field of cancer therapy owing to its good safety benefit. It has been found that H2 at a high concentration would inhibit cell mitochondrial respiration and break redox homeostasis, thus causing cancer cell apoptosis and damages. However, achieving significant and long-term H2 release in the tumor to produce the best anticancer therapeutic impact was still problematic. Therefore, for future clinical translation of H2 therapy, alternative relevant ways to achieve continuous and efficient H2 generation within the tumor in a safe manner are needed.
Galvanic cells are a typical electrochemical etching method that can be used to generate H2 gas spontaneously in the aqueous environment without an external power supply. Recently, the research group of Prof. Zhuang Liu, collaborated with Prof. Liang Cheng develops a micro-galvanic cell by in situ reduction of a small amount of platinum (Pt) on the surface of Mg rods. The obtained Mg-based galvanic cell (MgG) can be etched by water to allow the effective generation of H2 gas and Mg(OH)2. After implanting MgG rods into tumors, the continuous generation of H2 could inhibit mitochondrial respiration and impair redox homeostasis inside tumor cells, while the byproduct Mg(OH)2 could neutralize the acidic tumor microenvironment (TME). In tumors with MgG rods implantation, an increase in the infiltration of CD8+ T cells and a decrease in the number of immunosuppressive myeloid-derived suppressor cells (MDSCs) are observed, indicating the modulation of the immunosuppressive TME toward the immune-supportive one, which is favorable for antitumor therapy. This strategy shows tumor inhibition effects in 4T1 and CT26 murine tumor models, and a malignant patient-derived xenograft (PDX) model of human origin. They also demonstrate that H2 therapy approach employing MgG rods could reduce the size of rabbit tumors. This work suggests that the widely used implanted Mg metal may be employed for successful and long-lasting H2 therapy using a galvanic cell design.
The first author, Mr. Nailin Yang, is from FUNSOM, Soochow University.
Title: Magnesium galvanic cells produce hydrogen and modulate the tumor microenvironment to inhibit cancer growth
Authors: Nailin Yang, Fei Gong, Bo Liu, Yu Hao, Yu Chao, Huali Lei, Xiaoyuan Yang, Yuehan Gong, Xianwen Wang, Zhuang Liu* & Liang Cheng*
Link to paper: https://www.nature.com/articles/s41467-022-29938-6
Link to Prof. Zhuang Liu's group: http://nano.suda.edu.cn/lz/
Link to Prof. Liang Cheng's group: http://funsom.suda.edu.cn/80/82/c2735a32898/page.htm
Acknowledgement: This paper was partially supported by the National Research Programs of China (2021YFF0701800), National Natural Science Foundation of China (U20A20254, 52072253, 21927803, and 52032008), Collaborative Innovation Center of Suzhou Nano Science and Technology, the 111 Project, Joint International Research Laboratory of Carbon-Based Functional Materials and Devices, a Jiangsu Natural Science Fund for Distinguished Young Scholars (BK20211544) and Jiangsu Social Development Project (BE2019658), a Project Funded for Postgraduate Research and Practice Innovation Program of Jiangsu Province (KYCX21_2947), a China Postdoctoral Science Foundation (2021TQ0229), and Suzhou Key Laboratory of Nanotechnology and Biomedicine. L.C. was supported by the Tang Scholarship of Soochow University.
Editor: Guo Jia