Yang Nailin, Sun Shumin, Xu Jiachen, Gong Fei, Lei Huali, Hao Yu, Pei Zifan, Wang Chenya, Yu Qiao, Nie Jihu, Jiang Nan, Ni Caifang, Cheng Liang
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China.
Macao Institute of Materials Science and Engineering, Macau University of Science and Technology, Taipa, Macau SAR, 999078, China.
Adv Mater. 2025 Feb;37(8):e2414929. doi: 10.1002/adma.202414929. Epub 2025 Jan 7.
The cGAS-STING pathway is pivotal in initiating antitumor immunity. However, tumor metabolism, particularly glycolysis, negatively regulates the activation of the cGAS-STING pathway. Herein, Mn galvanic cells (MnG) are prepared via liquid-phase exfoliation and in situ galvanic replacement to modulate tumor metabolism, thereby enhancing cGAS-STING activation for bidirectional synergistic H-immunotherapy. The obtained MnG can be etched by water, enabling efficient and sustained generation of H gas and Mn. MnG not only activated and amplified the cGAS-STING pathway through the sustained release of Mn but also regulated tumor glucose metabolism to inhibit the expression of three prime repair exonuclease 2 (TREX2), thereby synergistically enhancing the activation of the cGAS-STING pathway. The injection of MnG into tumors resulted in a robust immune response, thereby providing favorable support for antitumor therapy. Consequently, the combination of MnG with immune checkpoint blockade therapy resulted in significant suppression of both primary tumors and distant tumors. Furthermore, the MnG-lipiodol dispersion exhibited remarkable efficacy in combination with transarterial embolization (TAE)-gas-immunotherapy in a rabbit orthotopic liver tumor model. The present study underscores the significance of employing a metal galvanic cell strategy for enhanced immunotherapy, thereby offering a novel approach for rational design of bioactive materials to augment immunotherapeutic effectiveness.
环鸟苷酸-腺苷酸合成酶-干扰素基因刺激蛋白（cGAS-STING）通路在启动抗肿瘤免疫中起关键作用。然而，肿瘤代谢，尤其是糖酵解，对cGAS-STING通路的激活具有负向调节作用。在此，通过液相剥离和原位电置换制备了锰原电池（MnG），以调节肿瘤代谢，从而增强cGAS-STING的激活，实现双向协同氢免疫治疗。所制备的MnG可被水蚀刻，能够高效且持续地产生氢气和锰。MnG不仅通过锰的持续释放激活并放大cGAS-STING通路，还调节肿瘤葡萄糖代谢以抑制三磷酸修复核酸外切酶2（TREX2）的表达，从而协同增强cGAS-STING通路的激活。将MnG注射到肿瘤中可引发强烈的免疫反应，从而为抗肿瘤治疗提供有力支持。因此，MnG与免疫检查点阻断疗法联合使用可显著抑制原发性肿瘤和远处肿瘤。此外，在兔原位肝肿瘤模型中，MnG-碘油分散体与经动脉栓塞（TAE）-气体免疫疗法联合使用显示出显著疗效。本研究强调了采用金属原电池策略增强免疫治疗的重要性，从而为合理设计生物活性材料以提高免疫治疗效果提供了一种新方法。
