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Photoactivatable metabolic warheads enable precise and safe ablation of target cells in vivo

Author

Listed:
  • Sam Benson

    (The University of Edinburgh)

  • Fabio Moliner

    (The University of Edinburgh)

  • Antonio Fernandez

    (The University of Edinburgh)

  • Erkin Kuru

    (Harvard Medical School
    Wyss Institute for Biologically Inspired Engineering)

  • Nicholas L. Asiimwe

    (Molecular Recognition Research Center, Korea Institute of Science and Technology (KIST) & Bio-Med Program KIST-School UST)

  • Jun-Seok Lee

    (Korea University College of Medicine)

  • Lloyd Hamilton

    (The University of Edinburgh)

  • Dirk Sieger

    (The University of Edinburgh)

  • Isabel R. Bravo

    (The University of Edinburgh)

  • Abigail M. Elliot

    (The University of Edinburgh)

  • Yi Feng

    (The University of Edinburgh)

  • Marc Vendrell

    (The University of Edinburgh)

Abstract

Photoactivatable molecules enable ablation of malignant cells under the control of light, yet current agents can be ineffective at early stages of disease when target cells are similar to healthy surrounding tissues. In this work, we describe a chemical platform based on amino-substituted benzoselenadiazoles to build photoactivatable probes that mimic native metabolites as indicators of disease onset and progression. Through a series of synthetic derivatives, we have identified the key chemical groups in the benzoselenadiazole scaffold responsible for its photodynamic activity, and subsequently designed photosensitive metabolic warheads to target cells associated with various diseases, including bacterial infections and cancer. We demonstrate that versatile benzoselenadiazole metabolites can selectively kill pathogenic cells - but not healthy cells - with high precision after exposure to non-toxic visible light, reducing any potential side effects in vivo. This chemical platform provides powerful tools to exploit cellular metabolic signatures for safer therapeutic and surgical approaches.

Suggested Citation

  • Sam Benson & Fabio Moliner & Antonio Fernandez & Erkin Kuru & Nicholas L. Asiimwe & Jun-Seok Lee & Lloyd Hamilton & Dirk Sieger & Isabel R. Bravo & Abigail M. Elliot & Yi Feng & Marc Vendrell, 2021. "Photoactivatable metabolic warheads enable precise and safe ablation of target cells in vivo," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22578-2
    DOI: 10.1038/s41467-021-22578-2
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    Cited by:

    1. Erkin Kuru & Jonathan Rittichier & Helena Puig & Allison Flores & Subhrajit Rout & Isaac Han & Abigail E. Reese & Thomas M. Bartlett & Fabio Moliner & Sylvie G. Bernier & Jason D. Galpin & Jorge March, 2024. "Rapid discovery and evolution of nanosensors containing fluorogenic amino acids," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Na Feng & Zhen Peng & Xin Zhang & Yiling Lin & Lianrui Hu & Lei Zheng & Ben Zhong Tang & Jing Zhang, 2024. "Strategically engineered Au(I) complexes for orchestrated tumor eradication via chemo-phototherapy and induced immunogenic cell death," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Eleni Nestoros & Fabio Moliner & Ferran Nadal-Bufi & Deborah Seah & M. Carmen Ortega-Liebana & Zhiming Cheng & Sam Benson & Catherine Adam & Larissa Maierhofer & Kostiantyn Kozoriz & Jun-Seok Lee & As, 2024. "Tuning singlet oxygen generation with caged organic photosensitizers," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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