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Amphiphilic Polyaspartamide Derivatives with Cholesterol Introduction Enhanced Ex Vivo mRNA Transfection Efficiency to Natural Killer Cells
- Authors
- Koam, David; Park, Ha Yeon; Kim, Dong Sun; Kwon, Hyeong Jin; Lee, Yan; Kim, Kyobum; Naito, Mitsuru; Kim, Hyun Jin
- Issue Date
- Jan-2025
- Publisher
- ACS Publications
- Keywords
- Cholesterol; Deoxyribonuclease; Diethylenetriamine; Gamma Interferon; Uridine Triphosphate; Cholesterol; Klrk1 Protein, Human; Nk Cell Lectin-like Receptor Subfamily K; Peptides; Rna, Messenger; Rneasy Mini Kit; Cancer Cells; Cell Culture; Cell Engineering; Cell Membranes; Fibroblasts; Amphiphilics; Antigen Receptors; Diethylenetriamine; Ex-vivo; Mrna Transfection; Natural Killer; Natural Killer Cells; Polyaspartamides; Transfection Efficiency; Cholesterol; Amphiphilic Polyaspartamide Derivative; Chimeric Antigen Receptor; Cholesterol; Cyclohexylethylamine; Deoxyribonuclease; Diethylenetriamine; Fusion Protein; Gamma Interferon; Messenger Rna; Natural Killer Cell Receptor Nkg2d; Plasmid Dna; Polymer; Polymer Nanoparticle; Unclassified Drug; Uridine Triphosphate; Klrk1 Protein, Human; Natural Killer Cell Lectin Like Receptor Subfamily K; Peptide; Amino Terminal Sequence; Antineoplastic Activity; Article; Cancer Cell; Cell Viability; Clinical Evaluation; Controlled Study; Endosome; Enzyme Linked Immunosorbent Assay; Ex Vivo Study; Fibroblast; Gene Overexpression; Gene Targeting; Genetic Transfection; Human; Human Cell; Hydrophobicity; Immune Response; Natural Killer Cell; Polymerization; Surface Area; Chemistry; Drug Effect; Genetics; Immunology; Metabolism; Procedures; Tumor Cell Line; Cell Line, Tumor; Humans; Killer Cells, Natural; Nk Cell Lectin-like Receptor Subfamily K; Peptides; Rna, Messenger; Transfection
- Citation
- Biomacromolecules, v.26, no.2, pp 1086 - 1097
- Pages
- 12
- Indexed
- SCIE
SCOPUS
- Journal Title
- Biomacromolecules
- Volume
- 26
- Number
- 2
- Start Page
- 1086
- End Page
- 1097
- ISSN
- 1525-7797
1526-4602
- Abstract
- Engineered natural killer (NK) cells eliminate cancer cells by overexpressing a chimeric antigen receptor, producing highly efficient and safe NK cell therapies. This study investigated the polyplex formulation for the fusion protein GreenLantern-natural killer group 2D (NKG2D) mRNA to evaluate its ex vivo delivery efficacy into NK cells, wherein NKG2D on the surface of NK cells recognized its counterpart NKG2D ligands on cancer cells. Amphiphilic polyaspartamide derivatives Chol-PAsp(DET/CHE) were prepared by adding cyclohexylethylamine (CHE) and diethylenetriamine (DET) in the side chains and cholesterol (Chol) at the alpha-terminus to enhance endosomal escapability and optimize hydrophobicity. Chol-PAsp(DET/CHE) significantly improved mRNA delivery efficacy into NK-92mi cells, explained by increased polyplex stability and improved cellular uptake of mRNA. The NKG2D-overexpressing NK-92mi cells exhibited high anticancer efficacy against human colon cancer cells without affecting the viability of fibroblasts. Therefore, Chol-PAsp(DET/CHE) could be a promising mRNA delivery carrier for the ex vivo engineering of NK cells.
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Related Researcher
- Kim, Kyo Bum
- College of Engineering (Department of Chemical and Biochemical Engineering)