Self-Assembly versus Coassembly: An Amphiphilic NIR-II Aggregation-Induced Emission Luminogen for Phototheranostics of Orthotopic Glioblastoma

Glioblastoma (GBM) is the most lethal form of malignant brain tumor, known for its high infiltration, aggressiveness, and poor prognosis. Second near-infrared (NIR-II, 1000–1700 nm) phototheranostic agents bring intriguing opportunities for GBM management owing to their noninvasive nature, controllability, and deeper tissue penetration. Herein, an amphiphilic NIR-II luminogen (PEG-TD) with aggregation-induced emission (AIE) characteristics, along with its hydrophobic counterpart (C6-TD), was meticulously synthesized. Specifically, PEG-TD nanoparticles (NPs), formed through straightforward self-assembly, exhibited superior stability, simplicity, robust reactive oxygen species production efficiency, and excellent photothermal conversion compared to C6-TD NPs, which were fabricated via coassembly with DSPE-mPEG, primarily attributed to the distinct molecular arrangements within the forming aggregates. The inherent advantages of PEG-TD NPs led to significant therapeutic efficacy against GL261 cells under 808 nm laser irradiation. Eventually, NIR-II fluorescence/photothermal duplex imaging-guided combined photodynamic/photothermal therapy was successfully performed in an orthotopic glioblastoma mouse model with minimal adverse effects.