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.