Checkpoint blockade and nanosonosensitizer- augmented noninvasive sonodynamic therapy combination reduces tumour growth and metastases in mice
Checkpoint blockade and nanosonosensitizer- augmented noninvasive sonodynamic therapy combination reduces tumour growth and metastases in mice
复制标题
检查点封锁和纳米声敏剂增强无创声动力疗法组合可减少小鼠肿瘤生长和转移
DOI：
10.1038/s41467-019-09760-3
复制
发表时间：
2019-05-02
影响因子：
16.6
通讯作者：
Chen, Yu
中科院分区：
文献类型：
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作者：
Yue, Wenwen;Chen, Liang;Chen, Yu
联合检查点阻断（如PD1/PD-L1）与传统的临床疗法可能受到副作用和低肿瘤治疗效果的阻碍，阻碍了广泛的临床转化。在这里，我们报告了一种基于纳米声纳增敏剂增强无创声动力治疗（SDT）与检查点阻断免疫治疗相结合的联合肿瘤治疗方式。纳米声纳增敏剂（HMME/R837@Lip）的所有成分均获得临床批准，其中脂质体作为载体共包封声纳增敏剂（血卟啉单甲基醚（HMME））和免疫佐剂（咪喹莫特（R837））。通过多种肿瘤模型，我们证明纳米声纳增敏剂增强SDT与抗pd - l1结合可诱导抗肿瘤反应，不仅可以阻止原发性肿瘤的进展，还可以阻止肺转移。此外，联合治疗策略提供了长期的免疫记忆功能，可以防止肿瘤消除后的肿瘤再挑战。因此，这项工作代表了一种基于免疫治疗的非侵入性肿瘤治疗方式的概念验证组合肿瘤治疗方法。
Combined checkpoint blockade (e.g., PD1/PD-L1) with traditional clinical therapies can be hampered by side effects and low tumour-therapeutic outcome, hindering broad clinical translation. Here we report a combined tumour-therapeutic modality based on integrating nanosonosensitizers-augmented noninvasive sonodynamic therapy (SDT) with checkpoint-blockade immunotherapy. All components of the nanosonosensitizers (HMME/R837@Lip) are clinically approved, wherein liposomes act as carriers to co-encapsulate sonosensitizers (hematoporphyrin monomethyl ether (HMME)) and immune adjuvant (imiquimod (R837)). Using multiple tumour models, we demonstrate that combining nanosonosensitizers-augmented SDT with anti-PD-L1 induces an anti-tumour response, which not only arrests primary tumour progression, but also prevents lung metastasis. Furthermore, the combined treatment strategy offers a long-term immunological memory function, which can protect against tumour rechallenge after elimination of the initial tumours. Therefore, this work represents a proof-of-concept combinatorial tumour therapeutics based on noninvasive tumours-therapeutic modality with immunotherapy.