4.8 Article

A Metal-Phenolic Nanosensitizer Performs Hydrogen Sulfide-Reprogrammed Oxygen Metabolism for Cancer Radiotherapy Intensification and Immunogenicity

Journal

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 18, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202200830

Keywords

Hydrogen Sulfide; Immunogenicity; Polyphenols; Radiotherapy; Reprogrammed Oxygen Metabolism; Semiconducting Polymers

Funding

  1. National Natural Science Foundation of China [NSFC 32171318]
  2. Faculty of Health Sciences, University of Macau
  3. Start-up Research Grant (SRG) of the University of Macau [SRG2018-00130-FHS]
  4. Science and Technology Development Fund, Macau SAR [0109/2018/A3, 0011/2019/AKP, 0113/2019/A2, 0103/2021/A]
  5. Shenzhen Science and Technology Innovation Commission
  6. Shenzhen-Hong Kong-Macau Science and Technology Plan C [SGDX20201103093600004]
  7. Proteomics, Metabolomics and Drug Development Core, Animal Research Core, and Biological Imaging and Stem Cell Core in the Faculty of Health Sciences, University of Macau

Ask authors/readers for more resources

A metal-phenolic nanosensitizer has been developed to enhance the efficacy of radiotherapy by reprogramming oxygen metabolism and increasing oxygen utilization efficiency. The nanosensitizer reduced cellular oxygen consumption rate and utilized preserved oxygen to intensify radiotherapy.
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 (H2S) 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 H2S 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.

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