Lutetium texaphyrin: A photocatalyst that triggers pyroptosis via biomolecular photoredox catalysis

Yunjie Xu, Calvin V. Chau, Jieun Lee, Adam C. Sedgwick, Le Yu, Mingle Li, Xiaojun Peng, Jong Seung Kim, Jonathan L. Sessler

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Photon-controlled pyroptosis activation (PhotoPyro) is a promising technique for cancer immunotherapy due to its noninvasive nature, precise control, and ease of operation. Here, we report that biomolecular photoredox catalysis in cells might be an important mechanism underlying PhotoPyro. Our findings reveal that the photocatalyst lutetium texaphyrin (MLu) facilitates rapid and direct photoredox oxidation of nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide phosphate, and various amino acids, thereby triggering pyroptosis through the caspase 3/GSDME pathway. This mechanism is distinct from the well-established role of MLu as a photodynamic therapy sensitizer in cells. Two analogs of MLu, bearing different coordinated central metal cations, were also explored as controls. The first control, gadolinium texaphyrin (MGd), is a weak photocatalyst but generates reactive oxygen species (ROS) efficiently. The second control, manganese texaphyrin (MMn), is ineffective as both a photocatalyst and a ROS generator. Neither MGd nor MMn was found to trigger pyroptosis under the conditions where MLu was active. Even in the presence of a ROS scavenger, treating MDA-MB-231 cells with MLu at concentrations as low as 50 nM still allows for pyroptosis photo-activation. The present findings highlight how biomolecular photoredox catalysis could contribute to pyroptosis activation by mechanisms largely independent of ROS.

Original languageEnglish
Article numbere2314620121
JournalProceedings of the National Academy of Sciences of the United States of America
Volume121
Issue number9
DOIs
Publication statusPublished - 2024 Feb 27

Bibliographical note

Publisher Copyright:
© 2024 the Author(s). Published by PNAS.

Keywords

  • NAD(P)H
  • NIR photocatalyst
  • PhotoPyro
  • photoredox catalysis
  • pyroptosis

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Lutetium texaphyrin: A photocatalyst that triggers pyroptosis via biomolecular photoredox catalysis'. Together they form a unique fingerprint.

Cite this