Journal
NANO LETTERS
Volume 21, Issue 19, Pages 8281-8289Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.1c02790
Keywords
biodegradable upconversion nanoparticle; pyroptosis; immunotherapy; osmolarity; ion overload
Categories
Funding
- Chinese Government [2017YFE0132300]
- National Natural Science Foundation of China [NSFC 51720105015, 51929201, 51922097, 51772124, 51872282, 52050077, 52102354, 52102180]
- Key Research Program of Frontier Sciences, CAS [YZDY-SSW-JSC018]
- Postdoctoral Innovative Talents Support Program [BX2021360]
- Australian Government [2017YFE0132300]
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This study proposes biodegradable K3ZrF7:Yb/Er upconversion nanoparticles (ZrNPs) as pyroptosis inducers for cancer immunotherapy, which can release ions to induce intracellular osmotic imbalance and trigger cell death mechanisms. In vivo tests confirm that ZrNPs-induced pyroptosis exhibits superior antitumor immunity activity, inhibiting tumor growth and pulmonary metastasis.
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-1 beta (IL-1 beta) 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.
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