Biodegradable Upconversion Nanoparticles Induce Pyroptosis for Cancer Immunotherapy

Pyroptosis, which is a mode of programmed cell death, has proven effective for cancer therapy. However, efficient pyroptosis inducers for tumor treatment are limited. This study proposes biodegradable K₃ZrF₇:Yb/Er upconversion nanoparticles (ZrNPs) as pyroptosis inducers for cancer immunotherapy. ZrNPs, which are similar to ion reservoirs, can be dissolved inside cancer cells and release high amounts of K⁺ and [ZrF₇]^3- ions, resulting a surge in intracellular osmolarity and homeostasis imbalance. This further induces an increase in reactive oxygen species (ROS), caspase-1 protein activation, gasdermin D (GSDMD) cleavage, and interleukin-1β (IL-1β) maturity, and results in cytolysis. In vivo tests confirm that ZrNPs-induced pyroptosis exhibits superior antitumor immunity activity confirmed by enhanced dendritic cells (DCs) maturity and frequency of effector-memory T cells, as well as observably inhibiting tumor growth and pulmonary metastasis. This work is believed to extend the biomedical applications of upconversion nanomaterials and deepen the understanding of intrinsic immunomodulatory activity of nanomaterials.