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

Authors
Shin, Ha EunHan, Jun-HyeokPark, Joo DongPark, MinjiHan, JieunKang, Min-HoLee, Jung SeungPark, Chun GwonPark, JuwonKim, Hyun-YoungCho, DuckPark, Wooram
Issue Date
2024-03
Publisher
John Wiley & Sons Ltd.
Citation
Advanced Functional Materials
Abstract
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
Keywords
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
ISSN
1616-301X
URI
https://pubs.kist.re.kr/handle/201004/149500
DOI
10.1002/adfm.202315721
Appears in Collections:
KIST Article > 2024
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE