An acid-activatable nanosensitizer library realizes tunable pyroptosis activation in tumors

Li, Mingle; Kim, Jungryun; Xu, Yunjie; Kim, Jong Seung

doi:10.1016/j.matt.2022.12.004

Cited by 3 publications

(1 citation statement)

References 9 publications

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“…In addition to localizing PS effectively to induce pyroptotic cancer cell death, it is essential to minimize adverse effects on healthy cells. In 2022, Chen and colleagues reported a library of acid-activable nanophotosensitizers ( ANPS ) that allowed for the off-on tuning of pyroptosis as the result of targeting the signaling of early endosomes (Figure b-vii). , By targeting both spatially and temporally distinct stages of endosomal maturation, ANPS allowed the regulation of cellular pyroptosis. ANPS consists of three components, namely a pH-sensitive copolymer, a PS (Ce6), and a quencher (QSY21).…”

Section: Design Of Photopyromentioning

confidence: 99%

Photon-Controlled Pyroptosis Activation (PhotoPyro): An Emerging Trigger for Antitumor Immune Response

Kim

Rha

et al. 2023

J. Am. Chem. Soc.

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Pyroptosis refers to the process of gasdermin-mediated lytic programmed cell death (PCD) characterized by the release of pro-inflammatory cytokines. Our knowledge of pyroptosis has expanded beyond the cellular level and now includes extracellular responses. In recent years, pyroptosis has attracted considerable attention due to its potential to induce host immunity. For instance, at the 2022 International Medicinal Chemistry of Natural Active Ligand Metal-Based Drugs (MCNALMD) conference, numerous researchers demonstrated an interest in photon-controlled pyroptosis activation ("PhotoPyro"), an emerging pyroptosis-engineered approach for activating systemic immunity via photoirradiation. Given this enthusiasm, we share in this Perspective our views on this emerging area and expound on how and why "PhotoPyro" could trigger antitumor immunity (i.e., turning so-called "cold" tumors "hot"). In doing so, we have tried to highlight cutting-edge breakthroughs in PhotoPyro while suggesting areas for future contributions. By providing insights into the current state of the art and serving as a resource for individuals interested in working in this area, it is hoped that this Perspective will set the stage for PhotoPyro to evolve into a broadly applicable cancer treatment strategy.

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Section: Design Of Photopyromentioning

confidence: 99%

Photon-Controlled Pyroptosis Activation (PhotoPyro): An Emerging Trigger for Antitumor Immune Response

Kim

Rha

et al. 2023

J. Am. Chem. Soc.

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Reinforcing the immunogenic cell death to enhance cancer immunotherapy efficacy

Xiao

et al. 2023

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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

Xu,

Chau,

Lee

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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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.

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An acid-activatable nanosensitizer library realizes tunable pyroptosis activation in tumors

Cited by 3 publications

References 9 publications

Photon-Controlled Pyroptosis Activation (PhotoPyro): An Emerging Trigger for Antitumor Immune Response

Photon-Controlled Pyroptosis Activation (PhotoPyro): An Emerging Trigger for Antitumor Immune Response

Reinforcing the immunogenic cell death to enhance cancer immunotherapy efficacy

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

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