Preclinical evaluation demonstrates that a novel type-I photosensitizer triggers pyroptosis and suppresses tumor growth in mice, highlighting a potent strategy to activate antitumor immunity.
Pyroptosis is a proinflammatory and lytic programmed cell death form, which can promote cytotoxic T lymphocyte (CTL) maturation and tumor infiltration through the release of damage-associated molecular patterns (DAMPs). Therefore, the induction of pyroptosis by small molecules is a promising strategy to activate antitumor immunity. In this work, we report the design of a new class of pyrazolo[1,5- a ]pyrimidine-based type-I photosensitizers (PSs) as efficient pyroptosis inducers for cancer photodynamic therapy (PDT). Among the compounds, ZS-3 exhibited the most excellent reactive oxygen species (ROS) generation ability and phototoxicity in vitro. It was found that ZS-3 induced cell pyroptosis through the caspase-3/gasdermin E (GSDME) pathway under light irradiation, characterized by bubble formation and damage-associated molecular pattern release. Furthermore, ZS-3 lipid nanoparticles significantly inhibited tumor growth and evoked antitumor immune responses in vivo.
No takes yet. Share an insight, caveat, or question.
Zhang et al. (2025) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: