Tumor oxygen microenvironment-tailored electron transfer-type photosensitizers for precise cancer therapy

Yiting Yang, Yafu Wang, Yang Liu, Kui Wang, Ge Wang, Yonggang Yang, Won Jun Jang, Tony James, Juyoung Yoon, Hua Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

The oxygen level in a tumor typically exhibits complex characteristics, ranging from mild hypoxia to moderate and even severe hypoxia. This poses significant challenges for the efficacy of photodynamic therapy, where oxygen is an essential element. Herein, we propose a novel therapeutic strategy and develop a series of lipid droplet-targeting photosensitive dyes (Ser-TPAs), i.e., in situ synergistic activation of two different electron transfer-type reactions. Based on this strategy, Ser-TPAs can synergistically generate O2˙− and nitrogen radicals regardless of the oxygen content, which results in a sustained high concentration of strongly oxidizing substances in the lipid droplets of cancer cells. As such, Ser-TPAs exhibited inhibitory activity against tumor growth in vivo, resulting in a significant reduction in tumor volume (Vexperimental group : Vcontrol group ≈ 0.07). This strategy offers a conceptual framework for the design of innovative photosensitive dyes that are suitable for cancer therapy in complex oxygen environments.
Original languageEnglish
Number of pages9
JournalChemical Science
Early online date7 Sept 2024
DOIs
Publication statusE-pub ahead of print - 7 Sept 2024

Data Availability Statement

The authors confirm that the data supporting the findings of this study are available within the article [and/or its ESI†].

Acknowledgements

T. D. J. wishes to thank the University of Bath and the Open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University (2020ZD01) for support. T. D. J. has been appointed as an Outstanding Talent by Henan Normal University. The work was supported by the Program for Innovative Research Team in Science and Technology at the University of Henan Province (23IRTSTHN002). All authors express their gratitude to Dr C. C. Shen for his invaluable assistance in this study.

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