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

Liang Zhang, An Song, Qi-Chao Yang, Shu-Jin Li, Shuo Wang, Shu-Cheng Wan, Jianwei Sun, Ryan T. K. Kwok, Jacky W. Y. Lam (), Hexiang Deng (), Ben Zhong Tang () and Zhi-Jun Sun ()
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Liang Zhang: Wuhan University
An Song: Wuhan University
Qi-Chao Yang: Wuhan University
Shu-Jin Li: Wuhan University
Shuo Wang: Wuhan University
Shu-Cheng Wan: Wuhan University
Jianwei Sun: The Hong Kong University of Science and Technology, Clear Water Bay
Ryan T. K. Kwok: The Hong Kong University of Science and Technology, Clear Water Bay
Jacky W. Y. Lam: The Hong Kong University of Science and Technology, Clear Water Bay
Hexiang Deng: Wuhan University, Luojiashan
Ben Zhong Tang: The Hong Kong University of Science and Technology, Clear Water Bay
Zhi-Jun Sun: Wuhan University

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract 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%.

Date: 2023
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DOI: 10.1038/s41467-023-41121-z

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