title: Cell Type Preference of a Novel Human Derived Cell-Permeable Peptide dNP2 and TAT in Murine Splenic Immune Cells.
abstract: Cell-permeable peptides (CPPs) have been widely studied as an attractive drug delivery system to deliver therapeutic macromolecules such as DNA, RNA, and protein into cells. However, its clinical application is still limited and controversial due to the lack of a complete understanding of delivery efficiency in target cells. Previously we identified and characterized the novel and superior CPP, named dNP2, and here we comparatively analyzed intracellular delivery efficiency of dNP2 and TAT in various immune cells of mouse spleen to demonstrate their cell type preference. dNP2- or TAT-conjugated fluorescent proteins were most efficiently taken up by phagocytic cells such as dendritic cells and macrophages while little protein uptake was seen by lymphocytes including T cells, B cells, and NK cells. Interestingly CD8+ lymphoid dendritic cells and CD62LloCD44hi memory like T cell subsets showed significantly better uptake efficiency in vitro and in vivo relative to other dendritic cells or T cells, respectively. In addition, activated macrophages, T cells, and B cells took up the proteins more efficiently relative to when in the resting state. Importantly, only dNP2, not TAT, shows significant intracellular protein delivery efficiency in vivo. Collectively, this study provides important information regarding heterogeneous intracellular delivery efficiency of CPPs such as dNP2 and TAT with cell type preference in the spleen needed for its application in phagocytic cells or activated immune cells.
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, 133-791, Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul, 133-791, Korea.
authors.forename: Sangho
authors.initials: S
authors.lastname: Lim
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, 133-791, Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul, 133-791, Korea.
authors.forename: Jung-Ah
authors.initials: JA
authors.lastname: Lee
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, 133-791, Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul, 133-791, Korea.
authors.forename: Ja-Hyun
authors.initials: JH
authors.lastname: Koo
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Korea.
authors.forename: Tae Gun
authors.initials: TG
authors.lastname: Kang
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Korea.
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Ha
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, 133-791, Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul, 133-791, Korea.
authors.forename: Je-Min
authors.initials: JM
authors.lastname: Choi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D057846:Cell-Penetrating Peptides / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D057846:Cell-Penetrating Peptides; D011994:Recombinant Proteins; C000606975:dNP2 peptide; D054322:tat Gene Products, Human Immunodeficiency Virus