Anionic Hofmeister Effect Differentiated Subcellular Distributions of pH‐Responsive Metal–Organic Cages for Tumor Photodynamic Immunotherapy
Abstract
Abstract The precise control of subcellular distribution offers significant advantages for advancing the understanding of cellular biology and targeted theranostics strategies. Herein, we report anionic Hofmeister effect triggered allostery of pH‐responsive metal–organic cage MOC‐68, which regulates the subcellular distributions with the salting‐out MOC‐68‐BF 4 exhibiting preferential cell membrane anchoring, while the salting‐in MOC‐68‐Cl demonstrating more endocytosis for lysosome targeting. Owing to the integration of multi‐functionalities of protonating imidazole moieties, conformationally adaptive amine vertices, and microsecond luminescent lifetimes into a nanocage, these MOCs show pH‐responsive singlet oxygen ( 1 O 2 ) generation through energy transfer pathways, and achieve microenvironment‐programmed photodynamic precision by anchoring MOC‐68‐BF 4 to near‐neutral cell membranes whereas enriching MOC‐68‐Cl in acidic lysosomes, which drives spatially resolved 1 O 2 generation gradients via protonation‐optimized metal‐to‐ligand charge transfer. Moreover, MOC‐68‐Cl achieves superior photocytotoxicity through PANoptosis‐mediated immunogenic cell death, driving primary tumor ablation via localized 1 O 2 burst while systemically activating T cell‐dependent adaptive immunity to concurrently suppress tumor progression and inhibit lung metastasis. This work highlights the potential of anion‐mediated biological behaviors of MOCs, providing a way to advance nanocage biomedicine for future precision theranostic applications.
Article Details
Authors (8)
Xiao‐Dong Zhang
MOE Laboratory of Bioinorganic and Synthetic Chemistry GBRCE for Functional Molecular Engineering, LIFM, IGCME, School of Chemistry Sun Yat‐Sen University 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 China
Yu‐Lin Lu
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 China
Yu Zhang
Xiangya Hospital, Central South University Changsha China
Wei‐Chun Li
Department MOE Laboratory of Bioinorganic and Synthetic Chemistry GBRCE For Functional Molecular Engineering LIFM IGCME School of Chemistry Sun Yat‐Sen University Guangzhou China
Mei Pan
Lehn Institute of Functional Materials, GBRCE for Functional Molecular Engineering, IGCME, School of Chemistry
Cheng‐Yong Su
GBRCE For Functional Molecular Engineering Lehn Institute of Functional Materials IGCME School of Chemistry Sun Yat‐Sen University Guangzhou P. R. China