Sun Shumin, Huang Xuan, Yang Nailin, Lei Huali, Pei Zifan, Han Zhihui, Liu Lin, Gong Fei, Yu Qiao, Li Jingrui, Chen Youdong, Cheng Liang
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China.
Macao Institute of Materials Science and Engineering, Macau University of Science and Technology, Taipa, Macau SAR 999078, China.
ACS Nano. 2024 Jul 15. doi: 10.1021/acsnano.4c05448.
Pyroptosis is an inflammatory form of programmed cell death associated with the immune system that can be induced by reactive oxygen species (ROS). As a therapeutic strategy with better penetration depth, sonodynamic therapy (SDT) is expected to induce pyroptosis of cancer cells and boost the immune response. However, it is still a limited problem to precisely adjust the structure of sonosensitizers to exhibit satisfactory sono-catalytic properties. Herein, fluorinated titanium oxide (TiOF) sonosensitizers were developed to induce pyroptosis under ultrasound (US) to boost antitumor immune responses, enabling highly effective SDT. On the one hand, the introduction of F atoms significantly reduced the adsorption energy of TiOF for oxygen and water, which is conducive to the occurrence of sono-catalytic reactions. On the other hand, the process of F replacing O increased the oxygen vacancies of the sonosensitizer and shortened the band gap, which enabled powerful ROS generation ability under US stimulation. In this case, large amounts of ROS could effectively kill cancer cells by inducing mitochondrial damage and disrupting oxidative homeostasis, leading to significant cell pyroptosis. Moreover, SDT treatment with TiOF not only suppressed tumor proliferation but also elicited robust immune memory effects and hindered tumor recurrence. This work highlighted the importance of precisely regulating the structure of sonosensitizers to achieve efficient ROS generation for inducing pyroptosis, which sets the stage for the further development of SDT-immunotherapy.
细胞焦亡是一种与免疫系统相关的程序性细胞死亡的炎症形式，可由活性氧（ROS）诱导。作为一种具有更好穿透深度的治疗策略，声动力疗法（SDT）有望诱导癌细胞发生细胞焦亡并增强免疫反应。然而，精确调整声敏剂的结构以展现出令人满意的声催化性能仍然是一个存在局限的问题。在此，开发了氟化钛氧化物（TiOF）声敏剂，以在超声（US）作用下诱导细胞焦亡，从而增强抗肿瘤免疫反应，实现高效的声动力疗法。一方面，F原子的引入显著降低了TiOF对氧气和水的吸附能，这有利于声催化反应的发生。另一方面，F取代O的过程增加了声敏剂的氧空位并缩短了带隙，使得在超声刺激下具有强大的ROS生成能力。在这种情况下，大量的ROS可通过诱导线粒体损伤和破坏氧化稳态有效地杀死癌细胞，导致明显的细胞焦亡。此外，用TiOF进行声动力疗法不仅抑制了肿瘤增殖，还引发了强大的免疫记忆效应并阻碍了肿瘤复发。这项工作突出了精确调节声敏剂结构以实现高效ROS生成以诱导细胞焦亡的重要性，为声动力疗法-免疫疗法的进一步发展奠定了基础。
