A Metal‐Phenolic Nanosensitizer Performs Hydrogen Sulfide‐Reprogrammed Oxygen Metabolism for Cancer Radiotherapy Intensification and Immunogenicity. Issue 18 (7th March 2022)

• Record Type: Journal Article
• Authors: Li, Jie; Xie, Lisi; Sang, Wei; Li, Wenxi; Wang, Guohao; Yan, Jie; Zhang, Zhan; Tian, Hao; Fan, Quli; Dai, Yunlu
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 18(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-07
• Subjects: Hydrogen Sulfide -- Immunogenicity -- Polyphenols -- Radiotherapy -- Reprogrammed Oxygen Metabolism -- Semiconducting Polymers; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202200830
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Radiotherapy (RT) is hampered by the limited oxygen in tumors, which could be potentiated via reprogramming the oxygen metabolism and increasing the oxygen utilization efficiency. Herein, a metal‐phenolic nanosensitizer (Hf‐PSP‐DTC@PLX) was integrated via an acid‐sensitive hydrogen sulfide (H2 S) donor (polyethylene glycol‐co‐polydithiocarbamates, PEG‐DTC) and a hafnium‐chelated polyphenolic semiconducting polymer (Hf‐PSP) in an amphiphilic polymer (poloxamer F127, PLX). Hf‐PSP‐DTC@PLX elicited a high imaging performance for precise RT and generated H2 S to reduce the cellular oxygen consumption rate via mitochondrial respiration inhibition, which reprogrammed the oxygen metabolism for improvement of the tumor oxygenation. Then, Hf‐sensitization could fully utilize the well‐preserved oxygen to intensify RT efficacy and activate immunogenicity. Such a synergistic strategy for improvement of oxygenation and oxygen utilization would have great potential in optimizing oxygen‐dependent therapeutics. Abstract : A NIR‐II fluorescence‐traced metal‐phenolic nanosensitizer was developed that performed H2 S‐reprogrammed oxygen metabolism for radiotherapy intensification and immunogenicity. Hf‐PSP‐DTC@PLX nanoparticles generate H2 S under an acidic tumor microenvironment to inhibit mitochondrial respiration and reprogram oxygen metabolism for tumor oxygenation. The chelated Hf ions simultaneously make full use of the preserved oxygen to improve the generation of local reactive oxygen species against tumor cells and to trigger antitumor immune activation.