Biodegradable Hydrogen Peroxide Nanogenerator for Controllable Cancer Immunotherapy Via Modulating Cell Death Pathway from Apoptosis to Pyroptosis

Abstract

Damage-associated molecular patterns (DAMPs) generated by dying tumor cells can react with host immune systems to activate autonomous immune responses. However, there are still huge challenges in achieving precise release of DAMPs for controllable cancer immunotherapy. As we all know, apoptosis is a process by which cells automatically end their lives determined by genes, and generally does not cause the strong release of DAMPs and immune responses. However, pyroptosis, as an emerging unique pathway of programmed cell death, can trigger a strong inflammatory response by generating large amount of DAMPs. Based on this, we prepared ZnO₂ as the donator of H₂O₂ to trigger pyroptosis and apoptosis by using high concentration of ZnO₂ (HZnO₂) and low concentration of ZnO₂ (LZnO₂) respectively, and further compared the different immune activation effects between these two cell death pathways. For the first time, we found HZnO₂ can induce pyroptosis effectively and its immune activation effect is better than that of apoptosis induced by LZnO₂. Therefore, this nanoplatform provides a new pyroptosis inducer and a new insight for understanding the relationship between cell death pathway and immune responses.

Keywords: pyroptosis, apoptosis, immunotherapy, ZnO2, autonomous immune response