声动力疗法（SDT）是一种很有前途的策略，作为一种“原位疫苗”，可增强实体瘤中抗肿瘤免疫反应的激活。然而，胰腺导管腺癌（PDAC）中致密的细胞外基质（ECM）导致缺氧和大多数药物的渗透受限，加剧了免疫抑制肿瘤微环境并限制了协同声动力免疫疗法的疗效。因此，调节ECM以缓解肿瘤缺氧并增强声动力免疫疗法对PDAC的疗效至关重要。CPIM纳米平台由巨噬细胞膜包被的氧气和药物递送系统（CM@PFOB-ICG-α-Mangostin）组成），采用超声波和挤出方法合成。通过近红外（NIR）成像和光声（PA）成像评估CPIM的体内同源靶向和缺氧缓解能力。还研究了 CPIM 纳米平台的肿瘤生长抑制潜力和重新编程肿瘤微环境的能力。α-Mangostin 的共同递送抑制 CAF 并增强基质消耗，从而促进大分子更好的浸润。此外，含有全氟化碳（PFC）的纳米乳剂可以靶向肿瘤细胞并通过同源靶向在肿瘤细胞内积累。超声波照射会导致氧气快速释放，成为缺氧肿瘤声动力疗法的潜在来源。此外，CPIM 重塑了免疫抑制微环境，增加了细胞毒性 T 淋巴细胞 (CTL) 的数量，并通过使用抗 PDL1 抗体阻断免疫检查点来增强其抗肿瘤免疫反应。本研究为联合免疫治疗提供了一种潜在的策略。输送氧气和α-Mangostin，旨在增强肿瘤的渗透以改善SDT。这种方法有效解决了实体瘤中免疫检查点阻断 (ICB) 治疗的现有局限性，同时通过协同声动力免疫疗法增强免疫反应。© 2024。作者获得 Springer-Verlag GmbH 德国独家许可，部分施普林格自然。

Sonodynamic therapy (SDT) is a promising strategy as an "in situ vaccine" to enhance activation of antitumor immune responses in solid tumors. However, the dense extracellular matrix (ECM) in pancreatic ductal adenocarcinoma (PDAC) lead to hypoxia and limited penetration of most drugs, aggravating the immunosuppressive tumor microenvironment and limiting the efficacy of synergistic sonodynamic immunotherapy. Therefore, it is essential to regulate ECM in order to alleviate tumor hypoxia and enhance the efficacy of sonodynamic immunotherapy for PDAC.The CPIM nanoplatform, consisting of a macrophage membrane-coated oxygen and drug delivery system (CM@PFOB-ICG-α-Mangostin), was synthesized using ultrasound and extrusion methods. The in vivo homologous targeting and hypoxia alleviation capabilities of CPIM were evaluated through near-infrared (NIR) imaging and photoacoustic (PA) imaging. The tumor growth inhibition potential and ability to reprogram the tumor microenvironment by the CPIM nanoplatform were also investigated.Co-delivery of α-Mangostin inhibits CAFs and enhances stromal depletion, thereby facilitating better infiltration of macromolecules. Additionally, the nanoemulsion containing perfluorocarbon (PFC) can target tumor cells and accumulate within them through homologous targeting. The US irradiation results in the rapid release of oxygen, serving as a potential source of sonodynamic therapy for hypoxic tumors. Moreover, CPIM reshapes the immunosuppressive microenvironment increasing the population of cytotoxic T lymphocytes (CTLs), and enhancing their anti-tumor immune response through the use of anti-PDL1 antibodies to block immune checkpoints.The present study offers a potential strategy for the co-delivery of oxygen and α-Mangostin, aiming to enhance the penetration of tumors to improve SDT. This approach effectively addresses the existing limitations of immune checkpoint blockade (ICB) treatment in solid tumors, while simultaneously boosting the immune response through synergistic sonodynamic immunotherapy.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.