https://doi.org/10.1016/j.apsb.2022.11.002
This new article publication from Acta Pharmaceutica Sinica B, discusses the co-delivery of nigericin and decitabine using hexahistidine-metal nanocarriers for pyroptosis-induced immunotherapeutics.
Pyroptosis provides a new window for relieving the tumor immunosuppressive microenvironment (TIM) and promoting systemic immune responses for tumor treatments. However, gasdermin D (GSDMD), a key protein in the pyroptosis process mediated by caspase-1, is low expressed in the majority of tumor cells and small-molecule inhibitors of DNA methylation suffer from nonspecific or single-function defects.
To address these issues, hexahistidine (His6)-metal assembly (HmA) was employed as the drug delivery vector to load nigericin (Nig) and decitabine (DAC) affording a dual-drug delivery system (Nig + DAC)@HmA. The (Nig + DAC)@HmA nanoparticles are efficiently internalized by cells through endocytosis, easily escape from the lysosome, and are highly distributed in the tumor sites. DAC up-regulates the expression of GSDMD which is then cleaved by the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and caspase-1 protein activated by Nig. Effective cancer cell pyroptosis is thus achieved and induces a significant systemic antitumor immunity for impressive tumor suppression with negligible side effects in vivo.
The results of this research suggest that such an easy-to-manipulate self-assembled nano-system (Nig + DAC)@HmA provides a new anticancer path by enhancing pyroptosis through reinforced inflammation.
Keywords: Self-assembled nanoparticle, Pyroptosis, NLRP3, GSDMD, InflammationIL-8, Immunotherapy responses, Solid tumor
Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383522004543-ga1_lrg.jpg
The mechanism of (Nig + DAC)@HmA cell pyroptosis for tumor immunotherapy. Pyroptotic cancer cells in primary tumor secret pro-inflammatory cytokines to reprogram tumor-associated macrophages from M2 to M1 for immunotherapy.
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The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association.
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CiteScore: 15.9
Impact Factor: 14.903
JIF without self-citation: 13.888
ISSN 2211-3835
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Article reference: Qiang Niu, Yu Liu, Yujing Zheng, Ziwei Tang, Yuna Qian, Ruogu Qi, Jianliang Shen, Ping Zhao, Co-delivery of nigericin and decitabine using hexahistidine-metal nanocarriers for pyroptosis-induced immunotherapeutics, Acta Pharmaceutica Sinica B, Volume 12, Issue 12, 2022, Pages 4458-4471, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2022.11.002