Phototherapeutic Agent for the Noninvasive Threatment of Glioblastoma

Glioblastoma is a type of fast-growing malignant brain tumor. It comes with significant treatment challenges, as the blood-brain barrier hinders the effective delivery of most therapeutic or diagnostic agents, and its high invasiveness can lead to poor outcomes with traditional treatment methods such as surgery and radiotherapy.

Phototheranostics can provide precise diagnosis and mild, yet efficient treatment of some cancers. A combination of fluorescence imaging and photoacoustic imaging within the second near-infrared window (NIR-II, 1000–1700 nm) can allow the accurate localization of deep-lying tumors. Simultaneously, photothermal therapy as a non-invasive, spatially selective, and rapid-response strategy could be useful for the treatment of the tumors. However, integrating these functions into a single, small molecule is challenging.

Qi-Wei Zhang, East China Normal University, Shanghai, China, and colleagues have designed and synthesized a versatile small-molecule phototherapeutic agent based on an aza-boron dipyrromethene (aza-BODIPY) scaffold (pictured). By modifying this scaffold with different electron-donating or electron-withdrawing substituents, the team obtained an optimized donor-acceptor-donor (D-A-D’)-type aza-BODIPY derivative, enabling NIR-II fluorescence emission at 1050 nm in an aqueous dispersion. The incorporation of a rotating unit (-CF₃) within the molecule led to efficient photothermal conversion (49.7 %) and high photoacoustic imaging performance.

Coating the aza-BODIPY derivative with folic acid-grafted polymers enabled crossing of the blood-brain barrier while simultaneously targeting glioma cells. This significantly enhanced the precision and efficiency of drug delivery. Overall, the developed nanodrug was successfully used for NIR-II fluorescence/photoacoustic dual-modal, imaging-guided photothermal therapy in glioblastoma-bearing mice. It enabled efficient tumor cell elimination with a single tail-vein injection and a single NIR laser irradiation.