Oxajulolidinyl‐Induced Molecular Twisting in Aza‐BODIPY Nanoplatform for NIR‐Triggered Synergistic Phototherapy of Glioblastoma

Glioblastoma (GBM) remains a formidable challenge in oncology due to its infiltrative nature and the blood‐brain barrier that impedes drug delivery. Herein, we report three novel oxajulolidinyl ( OJLD )‐functionalized aza‐BODIPY photosensitizers ( Ph‐OJLD , OMe‐OJLD , and CF 3 ‐OJLD ) designed for NIR‐triggered synergistic photodynamic and photothermal therapy. The OJLD moiety induces significant molecular distortion, as confirmed by single‐crystal X‐ray diffraction, which promotes reactive oxygen species generation and photothermal conversion. Ph‐OJLD self‐assembles into uniformly dispersed nanoplatforms (233 nm, polydispersity index = 0.11) with a negative surface charge (−46.1 mV). In vitro, laser‐activated Ph‐OJLD nanoparticles (NPs) suppress U251 cell proliferation and migration, induce mitochondrial damage, and trigger apoptosis. In an orthotopic GL261 glioma model, stereotactic injection of Ph‐OJLD NPs followed by NIR laser irradiation significantly reduces tumor size and enhances apoptosis without observable toxicity. This work establishes oxajulolidinyl modification as a promising strategy for designing multifunctional photosensitizers for GBM.