溶瘤腺病毒（OA）的治疗功效依赖于有效的病毒转导和复制。然而，许多肿瘤中柯萨奇腺病毒受体的有限表达以及细胞内抗病毒信号传导对 OA 感染和溶瘤造成了重大障碍。在这里，我们提出了配备声敏剂的OA（saOA），它通过声动力疗法增强病毒复制来增强溶瘤病毒疗法的抗肿瘤功效。 saOA不仅可以通过转铁蛋白受体介导的内吞作用有效感染肿瘤细胞，而且在超声照射下表现出增强的病毒复制和肿瘤溶瘤作用。我们发现，病毒上加载的声敏剂诱导肿瘤细胞内ROS的产生，从而触发JNK介导的自噬，最终导致病毒复制增强。在恶性黑色素瘤小鼠模型中，saOA 和声动力疗法的结合引发了强大的抗肿瘤免疫反应，从而显着抑制黑色素瘤生长并提高宿主存活率。这项工作凸显了声动力疗法在增强 OA 有效性方面的潜力，并为充分利用溶瘤病毒疗法的抗肿瘤功效提供了一个有前途的平台。

The therapeutic efficacy of oncolytic adenoviruses (OAs) relies on efficient viral transduction and replication. However, the limited expression of coxsackie-adenovirus receptors in many tumors, along with the intracellular antiviral signaling, poses significant obstacles to OA infection and oncolysis. Here, we present sonosensitizer-armed OAs (saOAs) that potentiate the antitumor efficacy of oncolytic virotherapy through sonodynamic therapy-augmented virus replication. The saOAs could not only efficiently infect tumor cells via transferrin receptor-mediated endocytosis but also exhibit enhanced viral replication and tumor oncolysis under ultrasound irradiation. We revealed that the sonosensitizer loaded on the viruses induced the generation of ROS within tumor cells, which triggered JNK-mediated autophagy, ultimately leading to the enhanced viral replication. In mouse models of malignant melanoma, the combination of saOAs and sonodynamic therapy elicited a robust antitumor immune response, resulting in significant inhibition of melanoma growth and improved host survival. This work highlights the potential of sonodynamic therapy in enhancing the effectiveness of OAs and provides a promising platform for fully exploiting the antitumor efficacy of oncolytic virotherapy.