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Checkpoint blockade and nanosonosensitizer-augmented noninvasive sonodynamic therapy combination reduces tumour growth and metastases in mice

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-019-09760-3

2041-1723

Wenwen Yue, Liang Chen, Luodan Yu, Bangguo Zhou, Haohao Yin, Weiwei Ren, Chang Liu, Le‐Hang Guo, Yifeng Zhang, Liping Sun, Kun Zhang, Hui‐Xiong Xu, Yu Chen,

Cancer Immunotherapy and Biomarkers

Abstract 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.