TY - JOUR
T1 - Lutetium texaphyrin: A photocatalyst that triggers pyroptosis via biomolecular photoredox catalysis
AU - Sedgwick, Adam
N1 - Publisher Copyright:
© 2024 the Author(s). Published by PNAS.
PY - 2024/2/27
Y1 - 2024/2/27
N2 - 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 mech-anism is distinct from the well- established role of MLu as a photodynamic therapy sen-sitizer 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 genera-tor. 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
AB - 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 mech-anism is distinct from the well- established role of MLu as a photodynamic therapy sen-sitizer 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 genera-tor. 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
UR - http://www.scopus.com/inward/record.url?scp=85185848541&partnerID=8YFLogxK
U2 - 10.1073/pnas.2314620121
DO - 10.1073/pnas.2314620121
M3 - Article
SN - 0027-8424
VL - 121
SP - e2314620121
JO - PNAS
JF - PNAS
IS - 9
M1 - e2314620121
ER -
