Lipid-based nanoparticles mimicking natural killer cells for triple- negative breast cancer therapy

Introduction: Immunotherapy combined with chemicals and genetic engineering tools is emerging as a promising strategy to treat triple-negative breast cancer (TNBC), which is more aggressive with poorer progress than other breast cancer subtypes. In this study, lipid-based nanoparticles (LNPs) possessed an NK cell-like function that could deliver tumor-specific therapeutics and regulate the tumor immune microenvironment. Method Our LNP mimicking NK cells consists of three characteristics: i) they are hydrophilic therapeutic substances so that genes can be included inside of LNP; ii) components that make up LNP themselves can exhibit therapeutic effects; and iii) specific membrane protein components of NK cells can be fabricated to the surface of LNP. These particles have both target-based delivery of HIC1 plasmid DNA and immune cell regulation functions. Results The drug delivery efficiency of LNP was maximized through the fusion of NK cell membrane protein, which can selectively target TNBC. We demonstrated that combining HIC1 restorations with C18-ceramide delivery can synergistically improve the treatment effect of TNBC. We confirmed that LNPs mimicking NK cells can activate immune cells and induce proinflammatory cytokines, which are known to influence antitumor immunity. Conclusion Delivered therapeutic genes can inhibit metastasis of TNBC and then induce apoptotic cell death while targeting macrophages to promote cytokine release. The anti-cancer effect is expected to apply to treating various difficult-to-treat cancers by LNP mimicking NK cells, which can simultaneously deliver therapeutic chemicals and genes.