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

Abstract

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.

Near-infrared metal agents assisting precision medicine: from strategic design to bioimaging and therapeutic applications

“…Pyroptosis is a regulated form of pro-inflammatory cell death that is characterized by the release of cytokines, damage, and pathogen-associated molecular patterns, as well as cell lysis. 323 Pyroptosis-induced inflammation has been found to enhance anti-tumor immunity and improve the effectiveness of immune checkpoint blocking (ICB). Unfortunately, the majority of current pyroptosis inducers are chemical agents.…”

Engineering Au44 Nanoclusters for NIR-II Luminescence Imaging-Guided Photoactivatable Cancer Immunotherapy

“…As reported, the PTT of in situ tumors can transform them from "cold" tumors into "hot" ones, thus promoting various immune cells to infiltrate the tumor site and trigger tumor-specific immune response. 54,55 Moreover, the PDT effect of the probe also synergistically contributes to tumor therapy. Besides, the photoactivatable release of NLG919 from Au 44 MBA 26 -NLG could reverse the immunosuppressive microenvironment, enhance tumor suppression, and also generate systemic immune memory to prevent tumor recurrence.…”

Activation of Pyroptosis Using AIEgen-Based sp2 Carbon-Linked Covalent Organic Frameworks

“…Inspired by the recent studies that pyroptosis is capable of triggering inflammatory storm in tumor tissues, which in turn recruits and activates the immune cells to turn the ″cold tumor ″ to ″hot tumor ″, − we hypothesized that the TPy-vinyl COF-mediated pyroptosis was able to promote immune response. Thus, the proportion of dendritic cells (DCs), the most powerful antigen-presenting cells for initiating the immune response, , was investigated using the flow cytometry system (FCM).…”