声动力治疗（Sonodynamic therapy，SDT）作为癌症免疫治疗的附加模式，增强了全身抗肿瘤免疫力。然而，基于传统聚焦超声（Focused ultrasound，FUS）的SDT介导的免疫治疗效率受到聚焦超声的微小聚焦区域的限制。聚焦声涡旋（Focused acoustic vortex，FAV）拥有更大的聚焦区域，可以引发比具有相同参数的聚焦超声更强的空化和热效应，有潜力克服这一问题。本研究调查了FAV介导的超声化疗联合免疫检查点阻断（Immune checkpoint blockade，ICB）在改变免疫抑制的肿瘤微环境（Tumor microenvironment，TME）中的可行性，抑制肿瘤生长和肺转移。声敏剂卡因E6（Chlorin e6，Ce6）和化疗药物多柔比星（Doxorubicin，Dox）共同装载到微泡-脂质体复合物中，形成Ce6/Dox@Lip@MBs（CDLM），用于“一体化”协同超声化疗，其主要成分经过临床批准。FAV激活的CDLM在肿瘤中显著丰富免疫原性细胞死亡诱导物，并与FUS激活的CDLM相比，增强了癌细胞的免疫原性细胞死亡。此外，增强的免疫原性细胞死亡和ICB联合应用，增加了细胞毒性T淋巴细胞和自然杀伤细胞的浸润以及极化M2巨噬细胞为M1巨噬细胞，降低了调节性T细胞。本研究为在肿瘤中丰富免疫原性细胞死亡诱导物并增强免疫原性细胞死亡提供了多功能策略，以改善免疫抑制的TME并增强全身抗肿瘤免疫力。版权所有© 2023 Elsevier Ltd. 保留所有权利。

Sonodynamic therapy (SDT) as an auxiliary modality of cancer immunotherapy enhances systemic anti-tumor immunity. However, the efficiency of SDT-mediated immunotherapy based on conventional focused ultrasound (FUS) is restricted by the tiny focal region of FUS. Focused acoustic vortex (FAV) possessing a larger focal region, can induce stronger cavitation and thermal effects than FUS with the same parameters, having the potential to overcome this issue. This research investigated the feasibility of FAV-mediated sonochemotherapy combined with the immune checkpoint blockade (ICB) to reshape immunosuppressive tumor microenvironment (TME), inhibit tumor growth and lung metastasis. Sonosensitizer chlorin e6 (Ce6) and chemotherapeutic agent doxorubicin (Dox) were co-loaded into microbubble-liposome complex to compose Ce6/Dox@Lip@MBs (CDLM) for "all-in-one" synergistic sonochemotherapy, whose main components were clinical approved. FAV-activated CDLM significantly enriched immunogenic cell death (ICD) inducers in tumors and amplified ICD of cancer cells compared with FUS-activated CDLM. Furthermore, the amplified-ICD combined with ICB increased the infiltration of cytotoxic T lymphocytes and natural killer cells, polarized M2 macrophages to M1 macrophages, and decreased regulatory T cells. This study provides a multifunctional strategy for enriching ICD inducers in tumors and amplifying ICD to ameliorate immunosuppressive TME and potentiate systemic anti-tumor immunity.Copyright © 2023 Elsevier Ltd. All rights reserved.