Activation of Pyroptosis Using AIEgen-Based sp² Carbon-Linked Covalent Organic Frameworks

Abstract

Covalent organic frameworks (COFs) have emerged as a promising class of crystalline porous materials for cancer phototherapy, due to their exceptional characteristics, including light absorption, biocompatibility, and photostability. However, the aggregation-caused quenching effect and apoptosis resistance often limit their therapeutic efficacy. Herein, we demonstrated for the first time that linking luminogens with aggregation-induced emission effect (AIEgens) into COF networks via vinyl linkages was an effective strategy to construct nonmetallic pyroptosis inducers for boosting antitumor immunity. Mechanistic investigations revealed that the formation of the vinyl linkage in the AIE COF endowed it with not only high brightness but also strong light absorption ability, long lifetime, and high quantum yield to favor the generation of reactive oxygen species for eliciting pyroptosis. In addition, the synergized system of the AIE COF and αPD-1 not only effectively eradicated primary and distant tumors but also inhibited tumor recurrence and metastasis in a bilateral 4T1 tumor model.

Self-Assembled Nanobiomaterials for Combination Immunotherapy

“…The COF-triggered pyroptosis significantly boosted the proportion of T-cell infiltration and diminished the number of immunosuppressive T reg -cells. Moreover, in combination with an αPD-1 blockade therapy COF, COF-mediated pyroptosis eliminated primary and distant tumors as well as prevented recurrence in a 4T1 tumor model …”

Covalent Organic Frameworks: Opportunities for Rational Materials Design in Cancer Therapy

“…[170d] Phototherapy is an effective stimulus for ICD, as confirmed using various COF systems. [170,[174][175] These systems use photosensitizing COFs to damage tumor cells via ROS generation or hyperthermia; the tumor cells then release DAMPs that activate antitumor immunity. In 2022, Sun and colleagues [170d] reported that COF-618-Cu, which exhibits CAT-like and glutathione peroxidase (GPX)-mimicking activity, enhances PDT and PTT by decomposing H 2 O 2 and oxidizing GSH, thereby eliciting a strong ICD response and remodeling the immune microenvironment (Figure 12C).…”

Biomaterials Elicit Pyroptosis Enhancing Cancer Immunotherapy

“…[120] Integrating luminogens with aggregation-induced emission effect into COF networks through vinyl ligations is an effective method to create nonmetallic pyroptosis inducers, ultimately boosting antitumor immunity (Figure 10a). [70] The formation of vinyl bonds in AIE COF results in high brightness, and strong light absorp-tion, which promotes the production of reactive oxygen species that causes pyroptosis (Figure 10b,c). In addition, A COF-919 is synthesized using a flat and distorted Aiegen-based motif.…”