免疫原性程序性细胞死亡，如火凤凰死和铁死，在有效诱导急性炎症反应和提升抗肿瘤免疫方面具有高效率。然而，对于能触发火凤凰死和铁死的双重诱导剂，特别是非金属诱导剂的探索仍然有限。本文展示了从平面和扭曲的AIEgen基团构建的共价有机框架（COF-919）作为一种诱导火凤凰死和铁死的双重诱导剂，以实现高效的抗肿瘤免疫。机制研究表明，COF-919具有更强的近红外光吸收、更低的能带能量和更长的寿命，有利于产生活性氧自由基（ROS）和光热转化，从而触发火凤凰死。由于其良好的ROS产生能力，它上调细胞内脂质过氧化，导致谷胱甘肽耗竭、谷胱甘肽过氧化物酶4表达降低，并诱导铁死。此外，COF-919诱导的火凤凰死和铁死有效抑制肿瘤转移和复发，导致超过90%的肿瘤生长抑制和治愈率超过80%。© 2023. Springer Nature Limited.

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%.© 2023. Springer Nature Limited.