DataVXAdvanced Functional MaterialsPaper
journal article·2024-07Open access

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

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

Advanced Functional Materials· Volume 34· Issue 30
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Source abstract

Abstract

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.
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Research context

Nanomaterials

OpenAlex topics: Immune Cell Function and Interaction · CAR-T cell therapy research · RNA Interference and Gene Delivery

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Integrative Biotechnology College of Biotechnology and Bioengineering Sungkyunkwan University (SKKU) Seobu‐ro 2066, Jangan‐gu Suwon Gyeonggi 16419 Republic of Korea

Department of Intelligent Precision Healthcare Convergence SKKU Institute for Convergence SKKU Seobu‐ro 2066, Jangan‐gu Suwon Gyeonggi 16419 Republic of Korea

Department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences and Technology (SAIHST) SKKU 115 Irwon‐ro, Gangnam‐gu Seoul 06355 Republic of Korea

Institute of Biotechnology and Bioengineering College of Biotechnology and Bioengineering SKKU Seobu‐ro 2066 Suwon Gyeonggi 16419 Republic of Korea

Biomedical and Chemical Engineering Department of Biotechnology The Catholic University of Korea 43 Jibong‐ro, Wonmi‐gu Bucheon Gyeonggi 14662 Republic of Korea

Department of Biomedical Engineering SKKU Seobu‐ro 2066, Jangan‐gu Suwon Gyeonggi 16419 Republic of Korea

Department of MetaBioHealth SKKU Institute for Convergence SKKU Seobu‐ro 2066, Jangan‐gu Suwon Gyeonggi 16419 Republic of Korea

Korea Institute of Science and Technology (KIST) 5 Hwarang‐ro 14‐gil, Seongbuk‐g Seoul 02792 Republic of Korea

Department of Tropical Medicine Medical Microbiology and Pharmacology John A. Burns School Medicine University of Hawai'i at Manoa Honolulu 96813 USA

Department of Laboratory Medicine and Genetics Samsung Medical Center SKKU School of Medicine SKKU 115 Irwon‐ro, Gangnam‐gu Seoul 06351 Republic of Korea

Department of Biopharmaceutical Convergence SKKU Seobu‐ro 2066, Jangan‐gu Suwon Gyeonggi 16419 Republic of Korea

Funding

National Research Foundation of Korea · Korea Health Industry Development Institute

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