Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan University, Wuhan 430072, China.
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China; Tianjin Institutes of Health Science, Tianjin 301600, China.
Biomaterials. 2025 Mar;314:122871. doi: 10.1016/j.biomaterials.2024.122871. Epub 2024 Oct 2.
Chimeric antigen receptor (CAR) T cell therapy is a highly effective immunotherapy for hematological tumors, but its efficacy against most solid tumors remains challenging. Herein, a novel synergistic combination therapy of drug-free triboelectric immunotherapy and CAR-T cell therapy against solid tumor was proposed. A triboelectric nanogenerator (TENG) that can generate pulsed direct-current by coupling triboelectrification effect and electrostatic breakdown effect was fabricated. The TENG can generate up to 30 pulse direct-current peaks with peak current output ≈35 μA in a single sliding to power the triboelectric immunotherapy. The pulsed direct-current stimulation induced immunogenic cell death of tumor cells (survival rate of 35.9 %), which promoted dendritic cells maturation, accelerated the process of antigen presentation to CAR-T cells and enhanced the systemic adaptive immune response. Furthermore, triboelectric immunotherapy promoted M1-like macrophage polarization, reduced regulatory T cells differentiation and reprogrammed the tumor immunosuppressive microenvironment, which ultimately enhanced the efficacy of CAR-T cells to eradicate nearly 60 % of NALM6 solid tumor mass. Notably, considering that triboelectric immunotherapy is a safe and effective drug-free antitumor strategy, the combined therapy did not increase the burden of double-medication on patients.
嵌合抗原受体 (CAR) T 细胞疗法是一种针对血液肿瘤的高效免疫疗法，但它对大多数实体瘤的疗效仍具有挑战性。在此，提出了一种新型的针对实体瘤的无药物摩擦电免疫疗法和 CAR-T 细胞疗法的协同联合治疗策略。本文构建了一种可通过摩擦起电效应和静电击穿效应耦合产生脉冲直流电的摩擦纳米发电机 (TENG)。TENG 可在单次滑动中产生高达 30 个脉冲直流电峰，其峰值电流输出约为 35 μA，可为摩擦电免疫疗法提供动力。脉冲直流电刺激诱导肿瘤细胞发生免疫原性细胞死亡（存活率为 35.9%），促进树突状细胞成熟，加速抗原呈递给 CAR-T 细胞的过程，并增强了全身适应性免疫反应。此外，摩擦电免疫疗法促进了 M1 样巨噬细胞极化，减少了调节性 T 细胞的分化，并重新编程了肿瘤免疫抑制微环境，最终增强了 CAR-T 细胞消除近 60%NALM6 实体瘤的疗效。值得注意的是，由于摩擦电免疫疗法是一种安全有效的无药物抗肿瘤策略，联合治疗并未增加双重药物治疗给患者带来的负担。
