Integration of AIEgens into Covalent Organic Frameworks for Pyroptosis and Ferroptosis Primed Cancer Immunotherapy

Abstract We report the construction of covalent organic framework (COF-919) from planar and twisted AIEgens-based motifs as a pyroptosis and ferroptosis dual-inducer that can elicit strong inflammatory response for efficient antitumor immunity. Mechanistic studies revealed that, in contrast to traditional COFs constructed with solely planar or twisted motifs, COF-919 displays stronger near-infrared light absorption, lower band energy and longer lifetime to favor the reactive oxygen species (ROS) generation and photothermal conversion for trigger pyroptosis. Because of its outstanding ROS production capability, intracellular lipid peroxidation was also upregulated to lead to glutathione depletion, glutathione peroxidase 4 low expression, and the induction of ferroptosis. Moreover, COF-919 induced pyroptosis and ferroptosis can effectively reshape the tumor immune microenvironment (TME) via promote T cells infiltration and relieve immunosuppressed TME to boost a T-cell-mediated immune response, which is favorable for inhibiting tumor metastasis and recurrence, with > 99% tumor growth inhibition and > 80% cure rates.