Xu Jiachen, Pei Zifan, Wang Yuanjie, Jiang Nan, Gong Yuehan, Gong Fei, Ni Caifang, Cheng Liang
Department of Vascular Surgery and Interventional Radiology, The Forth Affiliated Hospital of Soochow University, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, 215125, China; Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China.
Biomaterials. 2025 Jun;317:123063. doi: 10.1016/j.biomaterials.2024.123063. Epub 2024 Dec 26.
The development of novel microspheres for the combination of sonodynamic therapy (SDT) with transarterial embolization (TAE) therapy to amplify their efficacy has received increasing attention. Herein, a novel strategy for encapsulating sonosensitizers (e.g., oxygen-deficient manganese tungstate (MnWO) nanodots) with gelatin microspheres was proposed. The obtained MnWO-encapsulated microspheres (abbr. Mn-GMSs) facilitated efficient sonodynamic-embolization-metalloimmune therapy via the immune effects of metal ions on orthotopic liver cancer tumor after transarterial embolization (TAE). Due to the strong cavitation effect caused by the porous structure, Mn-GMSs exhibited a greater reactive oxygen species (ROS) generation rate than the free MnWO nanodots under US irradiation. Efficient SDT revealed robust cell-killing effects and triggered strong immunogenic cell death (ICD). Moreover, the Mn ions released from the bioactive Mn-GMSs further stimulated the dendritic cells (DCs) maturation and triggered the activation of the cGAS/STING pathway to enhance the immunological effect. Thus, Mn-GMSs achieved significant SDT therapeutic outcomes in H22 tumors in mice, and the combination of the Mn-GMSs triggered SDT with programmed cell death ligand 1 (PD-L1) antibodies could further enhance therapeutic outcomes. The Mn-GMSs exhibited high ROS generation efficacy under US irradiation, significant immune activation, good efficacy in combination with immune checkpoint inhibitor, and great potential for artery embolization-assisted drug delivery, thus enabling effective destruction of liver tumors in rats and rabbits. Therefore, this work provides a strategy for applying SDT in deep tumors and highlights a promising sonodynamic-embolization therapy for combating liver cancers.
开发用于将声动力疗法（SDT）与经动脉栓塞（TAE）疗法相结合以增强其疗效的新型微球受到了越来越多的关注。在此，提出了一种用明胶微球包裹声敏剂（如缺氧钨酸锰（MnWO）纳米点）的新策略。所获得的包裹MnWO的微球（简称Mn-GMSs）通过经动脉栓塞（TAE）后金属离子对原位肝癌肿瘤的免疫作用，促进了高效的声动力栓塞金属免疫疗法。由于多孔结构引起的强烈空化效应，Mn-GMSs在超声照射下比游离的MnWO纳米点表现出更高的活性氧（ROS）生成率。高效的SDT显示出强大的细胞杀伤作用并引发强烈的免疫原性细胞死亡（ICD）。此外，从生物活性Mn-GMSs释放的Mn离子进一步刺激树突状细胞（DCs）成熟并触发cGAS/STING途径的激活以增强免疫效果。因此，Mn-GMSs在小鼠H22肿瘤中取得了显著的SDT治疗效果，并且将Mn-GMSs引发的SDT与程序性细胞死亡配体1（PD-L1）抗体联合使用可以进一步提高治疗效果。Mn-GMSs在超声照射下表现出高ROS生成效率、显著的免疫激活、与免疫检查点抑制剂联合使用的良好效果以及动脉栓塞辅助药物递送的巨大潜力，从而能够有效破坏大鼠和兔子的肝脏肿瘤。因此，这项工作提供了一种在深部肿瘤中应用SDT的策略，并突出了一种用于对抗肝癌的有前景的声动力栓塞疗法。
