Ultrasound (US) becomes an appealing modality for stimulating or amplifying immune responses during cancer therapy, which is also termed sono-immunotherapy. However, the clinical prospect has not been fully realized due to the scarcity of efficient sonosensitizers. Herein, for the first time a novel Os-doped Au-tri(pyridin-4-yl) amine coordination structure (Os@Au-TPA)-based sonosensitizer is originally designed and synthesized for sono-immunotherapy of breast-metastasized tumors. Impressively, Os@Au-TPA shows much higher US-mediated ¹O₂-producing activity than Au-TPA as well as the other traditional sonosensitizers, for example, ≈41.6 folds to ce6, 19.5 times to Protoporphyrin IX (PpIX), 12.0 to Indocyanine Green (ICG), and 11.1 to Iron phthalocyanine (Pc(Fe)). The Os@Au-TPA can not only generate abundant ROS upon US irradiation to implement sonodynamic therapy (SDT), stimulating cell apoptosis and further immunogenic cell death, but can also generate O₂ to alleviate hypoxia to promote the polarization of M2 to M1 macrophages to enhance tumor immunogenicity. As a result, when combined with PD-L1 antibody, it remodels the immunosuppressive tumor microenvironment, achieves concurrent sonodynamic-triggered immune activation, and eradicates both the original and distant-metastasized tumors efficiently. This work not only provides a new strategy to construct potent sonosensitizers from pyridine-metal coordination structures but also proves that sonosensitizers with high performance are crucial in boosting cancer sono-immunotherapy.

中文翻译：

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一种用于肿瘤声Os@Au免疫疗法的高效 -TPA 配位结构增敏剂


超声 （US） 成为癌症治疗期间刺激或放大免疫反应的一种有吸引力的方式，也称为声波免疫疗法。然而，由于高效声敏剂的稀缺，临床前景尚未完全实现。在此，首次设计和合成了一种新型的基于 Os掺杂的 Au-三（吡啶-4-基）胺配位结构 （Os@Au-TPA） 的声敏剂，用于乳腺转移性肿瘤的声波免疫治疗。令人印象深刻的是，Os@Au-TPA 显示出比 Au-TPA 以及其他传统声敏剂高得多的 US 介导的 ¹O₂ 产生活性，例如≈，ce6 是 41.6 倍，是原卟啉 IX （PpIX） 的 19.5 倍，吲哚菁绿 （ICG） 是 12.0 倍，酞菁铁 （Pc（Fe）） 是 11.1 倍。Os@Au-TPA 不仅可以在 US 照射下产生丰富的 ROS 以实施声动力学疗法 （SDT），刺激细胞凋亡和进一步的免疫原性细胞死亡，还可以产生 O₂ 以缓解缺氧，促进 M2 向 M1 巨噬细胞的极化，从而增强肿瘤免疫原性。因此，当与 PD-L1 抗体结合时，它重塑免疫抑制性肿瘤微环境，实现同时声动力学触发的免疫激活，并有效根除原始和远处转移的肿瘤。这项工作不仅提供了一种从吡啶-金属配位结构构建有效声敏剂的新策略，而且还证明了高性能的声敏剂在促进癌症声波免疫治疗中至关重要。