Type-I AIE photosensitizer triggered cascade catalysis system for tumor targeted therapy and postoperative recurrence suppression

Aggregation-induced emission luminogens (AIEgens) based photodynamic therapy (PDT) has been emerging as a promising anti-cancer strategy. However, the short life span of many active oxygen species (ROS) reduces its therapeutic effect. Enhancing and maintaining the production of ROS in tumor cells remains a challenge. In this work, we constructed a tumor exosome bionic SAZs /AIEgens cascade catalysis system (CCS) for enhanced •OH generation and facilitating efficient tumor penetration. First, we prepared a Cu single atom nanozyme (Cu SAZs) with peroxidase activity, followed by coating with AIEgens absorbed tumor derived exosomes (TDE) to construct the CCS. The CCS system can penetrate tumor tissue after intravenous injection, and then TBP-2 generates •OH and hydrogen peroxide (H2O2) through type-1 PDT. Next, the H2O2 interacts with the Cu SAZs, resulting in the production of •OH in the tumor. The SGC-7901 tumor model experimental results revealed that the CCS systems significantly suppress tumor growth and efficiently cause tumor immunogenic cell death (ICD). CCS satisfies the requirement for enhanced and continuous generation of •OH, as well as compensates for the deficiency of H2O2 in SAZ-catalyzed therapy. More importantly, we found that CCS can effectively inhibit tumor recurrence in the CT26 recurrent mouse tumor model after surgery and has good clinical application potential.