Integration of AIEgens into covalent organic frameworks for pyroptosis and ferroptosis primed cancer immunotherapy

Immunogenic programmed cell death, such as pyroptosis and ferroptosis, efficiently induces an acute inflammatory response and boosts antitumor immunity. However, the exploration of dual-inducers, particularly nonmetallic inducers, capable of triggering both pyroptosis and ferroptosis remains limited. Here we show the construction of a covalent organic framework (COF-919) from planar and twisted AIEgen-based motifs as a dual-inducer of pyroptosis and ferroptosis for efficient antitumor immunity. Mechanistic studies reveal that COF-919 displays stronger near-infrared light absorption, lower band energy, and longer lifetime to favor the generation of reactive oxygen species (ROS) and photothermal conversion, triggering pyroptosis. Because of its good ROS production capability, it upregulates intracellular lipid peroxidation, leading to glutathione depletion, low expression of glutathione peroxidase 4, and induction of ferroptosis. Additionally, the induction of pyroptosis and ferroptosis by COF-919 effectively inhibits tumor metastasis and recurrence, resulting in over 90% tumor growth inhibition and cure rates exceeding 80%. Pyroptosis and ferroptosis are typically induced by metal species or chemotherapeutic drugs, and able to boost a robust antitumor immunity, however their therapeutic uses have been hindered by the risks arising from metal species or chemotherapeutic drugs. Here the authors report a pyroptosis and ferroptosis dual-inducer based on non-metallic AIEgen-based covalent organic frameworks.

Automated summary

This study presents a dual-inducer called COF-919, based on non-metallic AIEgen-based covalent organic frameworks, capable of triggering both pyroptosis and ferroptosis, resulting in enhanced anti-tumor immunity and inhibition of tumor growth and metastasis.