Wu Anbang, Jiang Lingdong, Xia Chao, Xu Qingqing, Zhou Bin, Jin Zhaokui, He Qianjun, Guo Jinxiao
Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200233, China.
School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, Guangdong, 518060, China.
Adv Sci (Weinh). 2023 Oct;10(28):e2303016. doi: 10.1002/advs.202303016. Epub 2023 Aug 16.
Tumor heterogeneity makes routine drugs difficult to penetrate solid tumors, limiting their therapy efficacies. Based on high tissue penetrability of hydrogen molecules (H ) and ultrasound (US) and the immunomodulation effects of H and lactic acid (LA), this work proposes a novel strategy of US-driven piezoelectrocatalytic tumor immunoactivation for high-efficacy therapy of deep tumors by piezoelectrocatalytic hydrogen generation and LA deprivation. A kind of US-responsive piezoelectric SnS nanosheets (SSN) is developed to realize US-triggered local hydrogen production and simultaneous LA deprivation in deep tumors. The proof-of-concept experiments which are executed on an orthotopic liver cancer model have verified that intratumoral SSN-medicated piezoelectrocatalytically generated H liberates effector CD8 T cells from the immunosuppression of tumor cells through down-regulating PD-L1 over-expression, and simultaneous LA deprivation activates CD8 T cells by inhibiting regulatory T cells, efficiently co-activating tumor immunity and achieving a high outcome of liver tumor therapy with complete tumor eradication and 100% mice survival. The proposed strategy of US-driven piezoelectrocatalytic tumor immunoactivation opens a safe and efficient pathway for deep tumor therapy.
肿瘤异质性使得常规药物难以穿透实体瘤，限制了它们的治疗效果。基于氢分子（H₂）和超声（US）的高组织穿透性以及H₂和乳酸（LA）的免疫调节作用，本研究提出了一种新型的超声驱动压电催化肿瘤免疫激活策略，通过压电催化产氢和乳酸剥夺来高效治疗深部肿瘤。开发了一种对超声响应的压电硫化锡纳米片（SSN），以实现超声触发深部肿瘤局部产氢并同时剥夺乳酸。在原位肝癌模型上进行的概念验证实验证实，瘤内SSN介导的压电催化产生的H₂通过下调程序性死亡配体1（PD-L1）的过表达，将效应性CD8⁺ T细胞从肿瘤细胞的免疫抑制中释放出来，同时乳酸剥夺通过抑制调节性T细胞来激活CD8⁺ T细胞，有效协同激活肿瘤免疫，实现了肝肿瘤治疗的高疗效，肿瘤完全根除且小鼠生存率达100%。所提出的超声驱动压电催化肿瘤免疫激活策略为深部肿瘤治疗开辟了一条安全有效的途径。
