Journal
BIOMATERIALS
Volume 280, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.121321
Keywords
Immunotherapy; Chemotherapy; Seleninic acid; NK cell; Selenoxide elimination reaction
Funding
- National Basic Research Program of China [2018YFA0208900]
- National Natural Science Foundation of China [21734006]
- Funds for Creative Research Groups of China of the National Natural Science Foundation of China [21821001]
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In this study, selenium-containing nanoparticles were constructed to synergistically enhance Pem-based chemotherapy and NK cell-based immunotherapy. The selenium compounds could deliver Pem to tumor sites and improve the chemotherapy efficiency. Additionally, they can also activate NK cell's immune response. The in vitro and in vivo experiments revealed the potential mechanism, highlighting the promising prospect of this strategy in chemoimmunotherapy.
NK cell-based immunotherapy and pemetrexed (Pem)-based chemotherapy have broad application prospects in cancer treatment. However, the over-expressed NK cell inhibitory receptor on the surface of cancer cells and the low cell internalization efficiency of Pem greatly limit their clinical application. Herein, we construct a series of selenium-containing nanoparticles to synergistically enhance Pem-based chemotherapy and NK cell-based immunotherapy. The nanoparticles could deliver Pem to tumor sites and strengthen the chemotherapy efficiency of Pem by seleninic acid, which is produced by the oxidation of beta-seleno ester. Moreover, seleninic acid can block the expression of inhibitory receptors against NK cells, thereby activating the immunocompetence of NK cells. The in vitro and in vivo experiments reveal the potential chemo-enhancing and immune-activating mechanism of seleninic acid, emphasizing the promising prospects of this strategy in effective chemoimmunotherapy.
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