A Highly Potent Os@Au-TPA Coordination Structure-Based Sonosensitizer for Tumor Sono-Immunotherapies

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 1 O 2 -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 O 2 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.