Enhancing CAR‐NK Cells Against Solid Tumors Through Chemical and Genetic Fortification with DOTAP‐Functionalized Lipid Nanoparticles

• DOI: 10.1002/adfm.202315721
• Publication Date: 2024-03-08T03:49:58Z
• Authors: Ha Eun Shin; Jun‐Hyeok Han; Joo Dong Park; Minji Park; Jieun Han; Min‐Ho Kang; Jung Seung Lee; Chun Gwon Park; Juwon Park; Hyun‐Young Kim; Duck Cho; Wooram Park
• Keywords: Cancer Immunotherapy

Abstract Natural killer (NK) cells are crucial in the innate immune response and show promise cancer immunotherapy, but face challenges activation targeted gene delivery. In this study, bifunctional lipid nanoparticles (DLNPs) containing 1,2‐dioleoyl‐3‐trimethylammonium‐propane (DOTAP), designed to bolster antitumor efficacy of chimeric antigen receptor‐modified NK (CAR‐NK) by facilitating efficient CAR mRNA delivery introduced. The DLNPs, created functionalizing FDA‐approved LNP compositions, exhibit excellent encapsulation colloidal stability. primed with DLNPs increased cytotoxicity against via extracellular signal‐regulated kinase/Mitogen‐Activated Protein Kinase pathway modulation mitochondrial dynamics changes. enter predominantly through clathrin‐mediated endocytosis, boosting overcoming cells' resistance genetic manipulation. CAR‐NK targeting glypican‐3, prevalent hepatocellular carcinoma, significant therapeutic effects an orthotopic mouse model. These findings underscore potential enhancing cell therapy for solid tumors, marking a stride cell‐based immunotherapy broadening prospects cell‐related disease interventions.