Most of chemotherapies are less effective when using alone. Exosomes (Exos) are cell derived nanovesicles that can serve as delivery nanoplatforms. Thus, Exos-based synergistic treatment is emerging as a promising strategy. Nevertheless, it is unknown about the underlying mechanism of Exos-based synergistic chemo-phototherapy at the gene level, especially in a glioma model. Here, we demonstrate that the combined therapy leads a superior chemo-phototherapy effect compared with chemotherapy or phototherapy alone. With the aid of Exos, the encapsulated agents can circulate for a longer time in vivo and effectively accumulated at tumor site. The local hyperthermia induced under near-infrared irradiation (NIR), impacts the permeability of Exos membrane and triggers drug release for maintaining a sustained chemotherapeutic efficacy. More importantly, the possible molecular mechanisms of Exos-based synergistic chemo-phototherapy are found to be involved in specific pathways including apoptosis, self-renewal repression and EMT program reversion. These data indicate that the engineered Exos can effectively combine chemotherapy and phototherapy to advance treatment of glioma and applied to other cancers as well, provide a new therapeutic strategy and potential molecular targets for clinical treatment.

单独使用时，大多数化学疗法效果较差。外来体（Exos）是细胞衍生的纳米囊泡，可以用作递送纳米平台。因此，基于Exos的协同治疗正在成为一种有前途的策略。然而，在基因水平上，特别是在神经胶质瘤模型中，关于基于Exos的协同化学光疗的潜在机制尚不清楚。在这里，我们证明了与单独的化学疗法或光疗相比，联合疗法具有更好的化学光疗效果。借助Exos，被包封的药物可以在体内循环更长的时间并有效地积累在肿瘤部位。在近红外辐射（NIR）下诱导的局部热疗会影响Exos膜的通透性并触发药物释放，以维持持续的化疗功效。更重要的是，发现基于Exos的协同化学光疗的可能分子机制与特定途径有关，包括凋亡，自我更新抑制和EMT程序还原。这些数据表明，经过工程改造的Exos可以有效地将化学疗法和光疗法结合起来以促进神经胶质瘤的治疗，并且也可以应用于其他癌症，为临床治疗提供新的治疗策略和潜在的分子靶标。