NIR-II Engineered Exosome Nanotheranostic Probes for “Oriented Blasting” in Orthotopic Glioblastoma

Glioblastoma (GBM), a highly aggressive and lethal brain tumor, presents a formidable clinical challenge due to its poor prognosis and lack of effective treatment options, underscoring the urgent need for innovative therapeutic strategies. Here, we report a promising phototheranostic platform based on a near-infrared II (NIR-II) organic molecule, MYM, which combines robust fluorescence with potent photothermal and photodynamic therapeutic capabilities. To maximize efficacy, MYM was encapsulated in exosomes derived from 293F cells and further functionalized with the iRGD peptide, enhancing both tumor targeting and penetration of the blood-brain barrier (MYM@iRGD-Exo). In vivo, studies demonstrate that MYM@iRGD-Exo can effectively penetrate the blood-brain barrier and selectively target GBM cells. Upon laser irradiation, it significantly inhibits tumor progression while promoting T-cell infiltration to enhance the immune response. Comprehensive RNA sequencing analyses revealed the activation of immune response pathways, highlighting the potential of this system to modulate antitumor immunity. This study offers an effective approach to glioblastoma therapy by integrating precision-targeted delivery, multimodal imaging, and synergistic therapeutic effects. The findings provide a theranostics platform aimed at overcoming current treatment limitations and improving clinical outcomes for cancer.