Nanobody modified high-performance AIE photosensitizer nanoparticles for precise photodynamic oral cancer therapy of patient-derived tumor xenograft

Photodynamic therapy (PDT) is a promising noninvasive treatment option for patients suffering from superficial tumors, such as oral cancer. However, for photosensitizers (PSs), it remains a grand challenge to simultaneously excel in all the key performance indicators including effective singlet oxygen (1O2) generation under clinical laser, specific targeting function and stable far-red (FR)/near-infrared (NIR) emission with low dark toxicity. In addition, traditional PS nanoparticles (NPs) for clinical use suffer from quenched fluorescence and reduced 1O2 production caused by molecular aggregation. To address these issues, AIEPS5 with aggregation-induced FR/NIR emission and effective 1O2 generation under 532 nm laser irradiation is designed by precise optimization of the chemical structure. By attaching a polyethylene glycol (PEG) chain onto AIEPS5, the yielded amphiphilic AIEPS5-PEG2000 can spontaneously self-assemble into water dispersible NPs, which are further endowed with targeted delivery function via the decoration of anti-Her-2 nanobody (NB). The bespoke AIEPS5-NPs-NB exhibit effective 1O2 generation capability, bright FR/NIR emission centered at 680 nm, and negligible dark toxicity, which outperform Heimbofen, a clinically approved PS in PDT using a patient-derived tumor xenograft model.