The heterogeneity and immunosuppression microenvironment of ovarian cancer seriously restrict the efficiency of monomodal treatment. Emerging multimodal therapy strategies based on sonodynamic therapy with enhanced antitumor effects have attracted intensive attention in the quest to combat cancer. However, exploring highly efficient sonosensitizers integrating chemodynamic/sonodynamic/immunotherapies with reversing immunosuppressive tumor microenvironment (TME) capacity is urgently desired but remains challenging. Here, a facile strategy is designed to synthesize immunomodulating sonocatalytic nanoagents (IrT-SCN) with dual-functional Ir-N centers and narrow bandgap for reversing immunosuppression and potentiating ovarian cancer immunotherapy. IrT-SCN with dual-functional centers Ir-N₂ and Ir-N₄ and conjugated networks show a reduced bandgap, moderate interaction with H₂O₂, and efficient production of reactive oxygen species (ROS). Such ROS capabilities include: 1) utilizing H₂O₂ in TME to catalytically generate potent O₂, as well as abundant superoxide anion (•O₂⁻) and singlet oxygen (¹O₂) radicals; 2) external ultrasound (US) irradiation can also boost the production of ¹O₂ simultaneously; 3) M1 polarization of tumor-associated macrophages and enhanced immune effect can promote the outcome of cancer treatment. This finding provides proof-of-concept evidence for the future development of immunomodulating sonocatalytic nanoagents for oncological treatments and other ROS-related biomedical fields.

中文翻译：

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具有双功能 Ir-N 中心和窄带隙的免疫调节声催化纳米制剂，用于逆转免疫抑制并增强卵巢癌免疫治疗


卵巢癌的异质性和免疫抑制微环境严重限制了单模式治疗的效率。基于声动力疗法的新兴多模式治疗策略具有增强的抗肿瘤作用，在对抗癌症的过程中引起了人们的广泛关注。然而，探索将化学动力学/声动力学/免疫疗法与逆转免疫抑制肿瘤微环境（TME）能力相结合的高效声敏剂是迫切需要的，但仍然具有挑战性。在这里，设计了一种简单的策略来合成具有双功能 Ir-N 中心和窄带隙的免疫调节声催化纳米制剂 (IrT-SCN)，用于逆转免疫抑制和增强卵巢癌免疫治疗。具有双功能中心 Ir-N ₂ 和 Ir-N ₄ 和共轭网络的 IrT-SCN 显示出带隙减小，与 H ₂ O < b3>，以及活性氧（ROS）的高效产生。此类ROS功能包括：1）利用TME中的H ₂ O ₂ 催化产生有效的O ₂ 以及丰富的超氧阴离子（•O ₂ ⁻ ) 和单线态氧 ( ¹ O ₂ ) 自由基； 2）外部超声（US）照射还可以同时促进 ¹ O ₂ 的产生； 3）肿瘤相关巨噬细胞的M1极化和增强的免疫效应可以促进癌症治疗的结果。这一发现为未来开发用于肿瘤治疗和其他 ROS 相关生物医学领域的免疫调节声催化纳米制剂提供了概念验证证据。