Concurrent Ferroptosis and Pyroptosis Induced by a Dual‐Organelle‐Targeted Type I/II AIE Photosensitizer for Bladder Cancer Immunotherapy
Abstract
Abstract The therapeutic efficacy and cell death modalities of photodynamic therapy (PDT) highly depend on reactive oxygen species (ROS) generation mediated by photosensitizers (PSs) and their subcellular localization. However, research exploring the potential mechanisms underlying ROS‐induced ferroptosis and pyroptosis remains scarce. In this study, we develop a type I/II aggregation‐induced emission photosensitizer (AIE PS), DFTBPPY (DY), that primarily accumulates in the endoplasmic reticulum (ER) and lipid droplets (LDs) to disrupt lipid homeostasis and induce concurrent cell death against bladder cancer. DY is selectively endocytosed by tumor cells and anchors in both ER and LDs. Upon laser irradiation, in situ DY can generate ROS to initiate oxidative stress and damage the functions of the ER and LDs. This disruption thereby initiates a lipid peroxidation‐cascading cell death pathway involving ferroptosis, pyroptosis, and immunogenic cell death (ICD), leading to potent antitumor effects. Our findings demonstrate that DY, as a dual‐organelle‐targeted PS, enhances therapeutic outcomes by orchestrating concurrent cell death mechanisms, which represents a promising alternative therapeutic strategy and highlights the potential of lipid imbalance in concurrent cell death for bladder cancer.
Article Details
Authors (14)
Yifan Cheng
Kun Zhou
Key Laboratory of Animal Virology, Ministry of Agricultural and Rural Affairs of China and Zhejiang Provincial Engineering Research Center of Animal Biological Products, Department of Veterinary Medicine, Zhejiang University College of Animal Sciences
Yuhang Chen
Center of Advanced Electrochemical Energy, State Key Laboratory of Advanced Chemical Power Sources, School of Chemistry and Chemical Engineering
Yibo Mei
Department of Urology The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 China
Zhongyu Wang
Wen‐Jin Wang
Clinical Translational Research Center of Aggregation‐Induced Emission The Second Affiliated Hospital School of Science and Engineering The Chinese University of Hong Kong Shenzhen Guangdong 518172 China
Haowen Li
Hangzhou Institute of Medicine
Yixuan Chen
Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology
Zonghang Liu
Guangdong Basic Research Center of Excellence for Aggregate Science, School of Science and Engineering, The Chinese University of Hong Kong (Shenzhen), Longgang, Shenzhen, Guangdong 518172, China
Jin Zeng
Yumei Luo
Dalin He
Department of Urology The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 China
Zheng Zhao
Ben Zhong Tang
School of Science and Engineering, Guangdong Basic Research Center of Excellence for Aggregate Science, The Chinese University of Hong Kong (Shenzhen), Longgang, Shenzhen 518172, Guangdong, P. R. China