A Highly Charged Positive Cage Causes Simultaneous Enhancement of Type‐II and O2‐Independent‐Type‐I Photodynamic Therapy via One‐/Two‐Photon Stimulation and Tumor Immunotherapy via PANoptosis and Ferroptosis
Xiao‐Dong Zhang,
Hui‐Juan Yu,
Shao‐Qi Guan,
Yu‐Lin Lu,
Yu Zhang,
Yin‐Hui Huang,
Ya‐Ping Wang,
Chen‐Hui Liu,
Zhong‐Min Cao,
Yu‐Han Qin,
Mei Pan,
Jun Shen,
Cheng‐Yong Su
Affiliations
Xiao‐Dong Zhang
Department MOE Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, LIFM, IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510275 China
Hui‐Juan Yu
Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology Guangdong Academy of Sciences Guangzhou 510275 China
Shao‐Qi Guan
Department MOE Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, LIFM, IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510275 China
Yu‐Lin Lu
Department MOE Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, LIFM, IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510275 China
Yu Zhang
Department MOE Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, LIFM, IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510275 China
Yin‐Hui Huang
Department MOE Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, LIFM, IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510275 China
Ya‐Ping Wang
Department of Radiology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat‐Sen Memorial Hospital Sun Yat‐Sen University Guangzhou 510030 China
Chen‐Hui Liu
Department MOE Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, LIFM, IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510275 China
Zhong‐Min Cao
Department MOE Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, LIFM, IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510275 China
Yu‐Han Qin
Department MOE Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, LIFM, IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510275 China
Mei Pan
Department MOE Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, LIFM, IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510275 China
Jun Shen
Department of Radiology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat‐Sen Memorial Hospital Sun Yat‐Sen University Guangzhou 510030 China
Cheng‐Yong Su
Department MOE Laboratory of Bioinorganic and Synthetic Chemistry, GBRCE for Functional Molecular Engineering, LIFM, IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510275 China
To solve the oxygen dependence problem of photodynamic therapy (PDT), it is critical to explore photosensitizers that do not rely on O2 molecule to generate reactive oxygen species (ROS). Herein, a stable cationic metal‐organic cage [Pd6(RuLoz3)8](BF4)28 (MOC‐88) that possesses high +28 charges is designed. The cage‐confined positive microenvironment enables efficient generation of hydroxyl radicals and improved yield of the singlet oxygen under one‐/two‐photon excitation, showing excellent performance to concurrently enhance Type‐II and O2‐independent‐Type‐I PDT. Moreover, the effective ROS production and robust lipid peroxidation trigger a series of signaling pathways (inflammasome, cyclic guanosine monophosphate–adenosine monophosphate synthase stimulator of interferon genes, and NF‐κB) to evoke PANoptosis and ferroptosis in tumor cells, enabling MOC‐88 to simultaneously cause the loss of cell membrane integrity, release a series of inflammatory cytokines and damage‐associated molecular patterns, stimulate the maturation and antigen presentation ability of dendritic cells, and ultimately activate T‐cell‐dependent adaptive immunity in vivo to inhibit tumor growth.
