Activation of Pyroptosis Using AIEgen-Based sp(2) Carbon-Linked Covalent Organic Frameworks

Covalentorganic frameworks (COFs) have emerged as a promisingclass of crystalline porous materials for cancer phototherapy, dueto their exceptional characteristics, including light absorption,biocompatibility, and photostability. However, the aggregation-causedquenching effect and apoptosis resistance often limit their therapeuticefficacy. Herein, we demonstrated for the first time that linkingluminogens with aggregation-induced emission effect (AIEgens) intoCOF networks via vinyl linkages was an effective strategy to constructnonmetallic pyroptosis inducers for boosting antitumor immunity. Mechanisticinvestigations revealed that the formation of the vinyl linkage inthe AIE COF endowed it with not only high brightness but also stronglight absorption ability, long lifetime, and high quantum yield tofavor the generation of reactive oxygen species for eliciting pyroptosis.In addition, the synergized system of the AIE COF and & alpha;PD-1not only effectively eradicated primary and distant tumors but alsoinhibited tumor recurrence and metastasis in a bilateral 4T1 tumormodel.

Automated summary

Covalent organic frameworks (COFs) have shown potential as porous materials for cancer phototherapy due to their unique characteristics. However, the aggregation-caused quenching effect and apoptosis resistance limit their effectiveness. This study demonstrated that linking AIEgens into COF networks was an effective strategy for inducing pyroptosis and enhancing antitumor immunity. The synergized system of AIE COF and αPD-1 effectively eradicated tumors and inhibited recurrence and metastasis in a tumor model.