Shin, Ha Eun Han, Jun-Hyeok Park, Joo Dong Park, Minji Han, Jieun Kang, Min-Ho Lee, Jung Seung Park, Chun Gwon Park, Juwon Kim, Hyun-Young Cho, Duck Park, Wooram 2024-03-21T08:00:11Z 2024-03-21T08:00:11Z 2024-03-21 2024-07 1616-301X https://pubs.kist.re.kr/handle/201004/149500 Natural killer (NK) cells are crucial in the innate immune response and show promise in cancer immunotherapy, but face challenges in activation and targeted gene delivery. In this study, bifunctional lipid nanoparticles (DLNPs) containing 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), designed to bolster the antitumor efficacy of chimeric antigen receptor-modified NK (CAR-NK) cells by facilitating activation and efficient CAR mRNA delivery are introduced. The DLNPs, created by functionalizing FDA-approved LNP compositions, exhibit excellent mRNA encapsulation and colloidal stability. NK cells primed with DLNPs show increased cytotoxicity against cancer cells via extracellular signal-regulated kinase/Mitogen-Activated Protein Kinase pathway modulation and mitochondrial dynamics changes. The DLNPs enter NK cells predominantly through clathrin-mediated endocytosis, boosting mRNA delivery and overcoming NK cells' resistance to genetic manipulation. CAR-NK cells targeting glypican-3, prevalent in hepatocellular carcinoma, show significant therapeutic effects in an orthotopic mouse model. These findings underscore the potential of DLNPs in enhancing CAR-NK cell therapy for solid tumors, marking a significant stride in NK cell-based cancer immunotherapy and broadening prospects for NK cell-related disease interventions. This study introduces dual-functional lipid nanoparticles to enhance the efficiency of chimeric antigen receptor-natural killer (CAR-NK) cells in cancer therapy. Optimized with a unique lipid, these nanoparticles significantly improve mRNA delivery and cell cytotoxicity, demonstrating promising results in treating hepatocellular carcinoma in a mouse model. image English John Wiley & Sons Ltd. Enhancing CAR-NK Cells Against Solid Tumors Through Chemical and Genetic Fortification with DOTAP-Functionalized Lipid Nanoparticles Article 10.1002/adfm.202315721 1 Advanced Functional Materials, v.34, no.30 Advanced Functional Materials 34 30 N scie scopus 001180236700001 2-s2.0-85186935034 Chemistry, Multidisciplinary Chemistry, Physical Nanoscience & Nanotechnology Materials Science, Multidisciplinary Physics, Applied Physics, Condensed Matter Chemistry Science & Technology - Other Topics Materials Science Physics Article ACUTE LYMPHOBLASTIC-LEUKEMIA MESSENGER-RNA DELIVERY CATIONIC LIPOSOME PLUS GEMCITABINE T-CELLS THERAPY EXPRESSION INDUCTION EFFICACY KINASE 1, 2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP) chimeric antigen receptor-natural killer (CAR-NK) cells hepatocellular carcinoma (HCC) lipid nanoparticles (LNPs) mRNA Delivery