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

Abstract

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 CF3-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.

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