Zinc ions trigger PANoptosis-like cell death in magnetic hyperthermia therapy of magnesium based implant for hepatocellular carcinoma.

Abstract

The treatment of hepatocellular carcinoma (HCC) is a worldwide urgent and pressing challenge. Magnetic hyperthermia therapy (MHT) is a relatively new therapeutic strategy for tumors in resent years, especially magnesium (Mg) implants with eddy thermal effect can be employed for MHT to therapy tumor. PANoptosis is a new type of programmed cell death (PCD), driven by Caspases and RIPKs through the formation of PANoptosomes. In our early study, we discovered Zn²⁺ came from Zn-LDH@Mg implant could induce pyroptosis. In this work, we further demonstrate that Zn²⁺ comes from Zn-LDH@Mg implant can induce PANoptosis-like cell death in MHT to therapy H22 cells and tumors, verified by immunofluorescence staining, TUNEL staining, western blot assay, ELISA and transcriptomics analysis. This work is the first time to combine MHT and PANoptosis to therapy HCC, emphasizing the importance of materials design for MHT, and providing a useful foundation for materials design combined with PCD to treat tumors.