Engineered exosome for NIR-triggered drug delivery and superior synergistic chemo-phototherapy in a glioma model

•A NIR-triggered Exos nano drug delivery platform was engineered simultaneously with curcumin and indocyanine green in this study.•The engineered Exo-CUR+ICG showed a superior chemo-phototherapy effect against glioma in vitro and in vivo, facilitating prevention of tumor rapid recurrence following transient phototherapy, and complete tumor remission.•The chemotherapy alone of Exos-CUR+ICG would cause cancer cell inhibition mainly by inducing apoptotic cells combined with cell arrest in G2/M phase, while synergistic chemo-phototherapy would directly cause cell necrosis to achieve superior anticancer effects.•The possible mechanisms of Exos-mediated chemo-phototherapy in a glioma model, at gene level, were found be involved in specific pathways including apoptosis, self-renewal repression and EMT program reversion. 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. [Display omitted]