PtNi nano trilobal-based nanostructure with magnetocaloric oscillation and catalytic effects for pyroptosis-triggered tumor immunotherapy

Pyroptosis, a unique form of programmed cell death, has been verified to be linked to inflammatory diseases and malignant tumors. Although great achievements have been made in pyroptosis research, several gaps, such as innate drug resistance and severe toxicity, hinder the development of pyroptosis inducers for biomedical applications. Thus, in this study, we designed a polyethylene glycol (PEG)ylated platinum-nickel (PtNi) bimetallic “trilobal”-shaped nanostructure (PPTNS) for effective pyroptosis-triggered tumor immunotherapy through a nanozyme catalytic and magnetocaloric oscillation dual strategy. Upon application of an alternating magnetic field, hyperthermia and mechanical oscillation of the specific sharp angles of PPTNS promoted damage-associated molecular pattern recognition, thereby activating the caspase-1-NLRP3-GSDMD pathway to increase cytokine recruitment. Furthermore, the high specific surface area and intrinsic nanozyme activities of PPTNS efficiently generated reactive oxygen species as the pathogen-associated molecular pattern, thus stimulating pattern recognition receptors to accelerate the oligomerization of the NOD-like receptor NLRP3. By this dual strategy, pyroptosis was triggered to perforate the cell membrane, resulting in cell rupture and cytokine release. After two weeks of treatment, the sizes of the breast tumors were significantly reduced without noticeable long-term toxicity in vivo. This strategy provides a magnetic-responsive platform for proptosis-triggered immunotherapy, which offers promising prospects for the highly efficient treatment of malignant tumors.