Perfluorocarbon nanodrug induced oxygen self-enriching sonodynamic therapy improves cancer immunotherapy after insufficient radiofrequency ablation

• DOI: 10.3389/fimmu.2023.1124152
• Publication Date: 2023-03-27T05:26:33Z
• Authors: Tongyi Huang; Wenxin Wu; Jiancong Wu; Yang Tan; Minru Zhang; Haiyi Long; Huanling Guo; Xiaoer Zhang; Wenwen Zhou; Qi Zhang; Xiaoyan Xie; Ming Xu; Chunyang Zhang
• Keywords: Sonodynamic therapy; Immunogenic cell death; Immunosuppression; Tumor progression; Immune checkpoint

Residual lesions and undetectable metastasis after insufficient radiofrequency ablation (iRFA) are associated with earlier new metastases poor survival in cancer patients, for induced aggressive tumor phenotype immunosuppression. Programmed cell death protein 1(PD-1) blockade has been reported to enhance the ablation-elicited antitumor immunity, but its ability eliminate incompletely ablated residual questioned. Here, we report a combined treatment modality post iRFA based on integrating an oxygen self-enriching nanodrug PFH-Ce6 liposome@O 2 nanodroplets (PCL@O )-augmented noninvasive sonodynamic therapy (SDT) PD-1 blockade. PCL@O containing Ce6 as sonosensitizer PFH O reservoir, was synthesized augmented SDT nanoplatform showed increased ROS generation raise effective apoptosis of cells, which also exposed more calreticulin induce stronger immunogenic (ICD). Combining iRFA, this optimized better anti-tumor response MC38 bearing mouse model, not only arrested primary progression, inhibited growth distant tumor, therefore prolonging survival. Profiling immune populations within draining lymph nodes tumors further revealed that combination effectively ICD, promoted maturation dendritic infiltration T well activation cytotoxic lymphocytes. While alone could result increase regulatory cells (Tregs) tumors, plus reduced number Tregs both tumors. Moreover, significantly initiate long-term memory, manifesting elevated levels CD8 + CD4 central memory cells. Therefore, study establishes preclinical proof concept apply augment immunotherapy iRFA.