Patient-Derived Microvesicles/AIE Luminogen Hybrid System for Personalized Sonodynamic Cancer Therapy in Patient-Derived Xenograft Models

Sonodynamic therapy (SDT), as an efficient way of tumor treatment, has the advantages of deep tumor penetration and high therapeutic efficacy. However, developing efficient sonosensitizers are still challenging. AIEgen-based SDT has never been reported and it is urgent to develop novel AIEgen-active sonosensitizers. Furthermore, the AIEgen-based theranostic system is promisingly needed to be proved on PDX models to be closer to the clinic. Herein, we constructed the first AIEgen based SDT system and found that DCPy has advantages over traditional sonosensitizers in SDT. Then, a patient-derived MVs/AIEgen hybrid system prepared by electroporation was used for personalized SDT in bladder cancer patient-derived xenograft (PDX) models. Impressively, AMVs displayed the superior tumor targeting ability and efficient personalized SDT therapy on PDX models, both of which were much more improved compared with PLGA/AIEgens nanoparticles and cell line-derived micro vesicles. This work presented the first example of an AIEgen-based hybrid system as sonosensitizer for SDT and provides new ideas for both the design of AIE-active sonosensitizers and the SDT treatment of cancers, further expanding the potential clinical application of AIEgens in the future.