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.