Cationic Nanoparticle-Mediated Activation of Natural Killer Cells for Effective Cancer Immunotherapy.

Abstract

Natural killer (NK) cells have been recognized as a next-generation therapy for cancer as they are less likely to trigger adverse events (e.g., cytokine storm or graft-versus-host disease) than T cell-based therapeutics. Although NK cell activation strategies through genetic engineering and cytokine treatment have been actively studied for successful cancer treatment, the approaches are inefficient, expensive, and involve complex processing. Here, we developed a facile and efficient method of activating NK cells using cationic nanoparticles (cNPs). The cytotoxic activity of cNP-treated primary NK and NK-92MI cells against triple-negative breast cancer cells was over 2-fold higher than that of control NK cells in vitro. Molecular biological analyses confirmed that cNPs altered the expression of CCR4 and CXCR4 of NK cells that function as chemokine receptors. In vitro live cell imaging showed that the NK cells treated with cNPs were better than control NK cells at interacting with cancer cells. Consistent with these in vitro results, cNP-treated NK cells effectively inhibited tumor growth in an in vivo tumor animal model of triple-negative breast cancer. Additionally, NK cells treated with cNPs were tracked effectively in vivo by magnetic resonance imaging. Thus, cNP-mediated activation of NK cells has great potential as an NK cell-based cancer immunotherapy. Most of all, activating NK cells using cNPs has a great advantage over conventional methods in that immune cells can be activated by a one-step facile process with exogenously charged nanomaterials, without the need for genetic engineering or cytokine treatment.