Intratumoral immunosuppressive microenvironment (ISM) remains the dominant limitation to disable oncological immunotherapy such as immunogenic cell death (ICD). To resolve the immune escape, a sonodynamic therapy (SDT)-based nanoplatform featuring continuous CO bubbling has been engineered to enforce continuous ultrasound-triggered inertial cavitation (UIC) for augmenting ROS production. Systematic and results demonstrate that the continuous UIC expedites massive production of reactive oxygen species (ROS), consequently enabling multiple enhancements of SDT under only one administration. More significantly, the highly-accumulative ROS arising from continuous UIC have been demonstrated to induce robust ICD that is typically represented by more antigen exposure and presentation, augmented DCs maturation and more activated effector CD8 T cells infiltration &. Concurrently, the most ISM alleviation releasing more pro-inflammatory cytokines and facilitating pro-tumorigenic M2-like macrophage polarization into anti-tumorigenic M1-like counterparts is accompanied, enabling immune escape blockade. Contributed by the significant ISM alleviation and massive ROS production for enhancing SDT and ICD, such SDT-based composite nanoplatforms harvest the most substantially enhanced inhibitory consequences against primary and metastatic tumors, which, thus, provide a profound attribute for T cell-based immunotherapy against tumor.

中文翻译：

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连续惯性空化激发大量活性氧，增强声动力疗法和针对乳腺癌的免疫原性细胞死亡

瘤内免疫抑制微环境（ISM）仍然是阻碍免疫原性细胞死亡（ICD）等肿瘤免疫治疗的主要限制。为了解决免疫逃逸问题，我们设计了一种基于声动力疗法 (SDT) 的纳米平台，该平台具有连续 CO 鼓泡功能，可强制执行连续超声波触发的惯性空化 (UIC)，以增加 ROS 的产生。系统性结果表明，连续 UIC 可以加速活性氧 (ROS) 的大量产生，从而只需一次给药即可实现 SDT 的多重增强。更重要的是，连续 UIC 产生的高度积累的 ROS 已被证明可以诱导强大的 ICD，这通常表现为更多的抗原暴露和呈递、增强的 DC 成熟和更多激活的效应 CD8 T 细胞浸润。同时，大多数 ISM 缓解会释放更多促炎细胞因子，并促进促肿瘤 M2 样巨噬细胞极化为抗肿瘤 M1 样巨噬细胞，从而实现免疫逃逸阻断。得益于显着的 ISM 缓解和大量 ROS 产生以增强 SDT 和 ICD，这种基于 SDT 的复合纳米平台获得了对原发性和转移性肿瘤最显着增强的抑制效果，从而为基于 T 细胞的免疫疗法提供了深刻的属性。瘤。