Fiber Optic‐Mediated Type I Photodynamic Therapy of Brain Glioblastoma Based on an Aggregation‐Induced Emission Photosensitizer

Abstract Glioblastoma (GBM) is one of the most lethal human malignancies. The current standard‐of‐care is highly invasive with strong toxic side effects, leading to poor prognosis and high mortality. As a safe and effective clinical approach, photodynamic therapy (PDT) has emerged as a suitable option for GBM. Nevertheless, its implementation is significantly impeded by the limits of light penetration depth and the firm reliance on oxygen. To overcome these challenges, herein, a promising strategy that harnesses a modified optical fiber and less oxygen‐dependent Type I aggregation‐induced emission (AIE) photosensitizer (PS) is developed for the first time to realize in vivo GBM treatments. The proposed AIE PS, namely TTTMN, characterized by a highly twisted molecular architecture and a bulky spacer, exhibits enhanced near‐infrared emission and strong production of hydroxyl and superoxide radicals at the aggregated state, thus affording efficient fluorescence imaging‐guided PDT once formulated into nanoparticles. The inhibition of orthotopic and subcutaneous GBM xenografts provides compelling evidence of the treatment efficacy of Type I PDT irradiated through a tumor‐inserted optical fiber. These findings highlight the substantially improved therapeutic outcomes achieved through fiber optic‐mediated Type I PDT, positioning it as a promising therapeutic modality for GBM.