Pyroptosis is an inflammatory form of programmed cell death (PCD) that is regulated by the Gasdermin protein family in response to various stimuli, playing a critical role in the development of tumor therapy strategies. However, cancers are generally known to escape from PCD via immunosuppressive pathways or other resistant mechanisms. In this study, an acid-responsive Fe/Mn bimetal-organic framework nanosystem carrying metal ions and immune adjuvant R848 (FeMn@R@H) was designed for combining pyroptosis and augmented immunotherapy. The FeMn@R@H would be triggered to disintegrate and release Fe3+ and Mn2+ ions in response to the acidic tumor microenvironment (TME), thereby initiating Fenton-like reactions for ROS-mediated pyroptosis. On the one hand, the pyroptosis-caused cell rupture would induce the release of proinflammatory cytokines and immunogenic constituents from tumor cells, further resulting in immunogenic cell death (ICD) to promote antitumor immune responses. On the other hand, the co-delivered R848 could reverse suppressive tumor immune microenvironment (TIME) and induce inflammatory responses by activating the TLR7/8 pathway. In conclusion, this tumor-specific therapy system can co-deliver metal ions and R848 to tumor tissues to perform pyroptosis-mediated PCD and augmented anti-tumor immunotherapy.
Congratulations to Professors Zhiqiang Yu and Meng Yu from Southern Medical University (Guangzhou, China) for their wonderful work published in Biomaterials (IF=15.30)!
InvivoChem is proud to provide Professors Zhiqiang Yu & Meng Yu with our high-quality product Resiquimod (R848)(Cat #: V1867; CAS #: 144875-48-9, TLR 7/8 agonist)for this research.
References: Biomaterials. 2023 Sep 16;302:122333. doi: 10.1016/j.biomaterials.2023.122333.