AIEgen-based nanotherapeutic strategy for enhanced FLASH irradiation to prevent tumour recurrence and avoid severe side effects

Compared with conventional radiotherapy, ultrahigh dose-rate (FLASH) radiotherapy spares normal tissues through oxygen exhaustion. However, residual cancer stem cells (CSCs) may generate tumour cells, causing tumour recurrence, which represents a critical problem after radiotherapy. Here we developed platelet cell membrane-camouflaged hollow TaOx nanospheres encapsulated with aggregation-induced emission luminogens (AIEgen) (named TPT). With characteristics derived from platelets, TPT nanoparticles (NPs) specifically target tumour regions and enhance FLASH radiotherapy via promoting the photoelectric effect by high Z-element tantalum and elevating reactive oxygen species levels through AIEgen-mediated photodynamic therapy (PDT). Under FLASH radiotherapy, TPT NPs exhibited a remarkable CSC killing effect, significantly inhibiting tumour recurrence. More important, compared with conventional radiotherapy, TPT NPs-promoted FLASH radiotherapy to efficiently eliminate tumours while reducing reoccurrence and severity of complications affecting normal tissues. This strategy provides a novel design to suppress tumour recurrence as well as to avoid adverse side effects.