1. Multifunctional nanoparticles for genetic engineering and bioimaging of natural killer (NK) cell therapeutics.
- Author
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Kim, Kwang-Soo, Han, Jun-Hyeok, Park, Jung-Hoon, Kim, Hyung-Keun, Choi, Seung Hee, Kim, Gyeong Ryeong, Song, Haengseok, An, Hee Jung, Han, Dong Keun, Park, Wooram, and Park, Kyung-Soon
- Subjects
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KILLER cells , *GENETIC engineering , *CHIMERIC antigen receptors , *CATIONIC polymers , *MYCOSIS fungoides , *GENE delivery techniques , *THERAPEUTICS , *TRAFFIC monitoring - Abstract
Recently, natural killer (NK)-based immunotherapy has attracted attention as a next-generation cell-based cancer treatment strategy due to its mild side effects and excellent therapeutic efficacy. Here, we describe multifunctional nanoparticles (MF-NPs) capable of genetically manipulating NK cells and tracking them in vivo through non-invasive magnetic resonance (MR) and fluorescence optical imaging. The MF-NPs were synthesized with a core-shell structure by conjugation of a cationic polymer labeled with a near-infrared (NIR) fluorescent molecule, with the aid of a polydopamine (PDA) coating layer. When administered to NKs, the MF-NPs exhibited excellent cytocompatibility, efficiently delivered genetic materials into the immune cells, and induced target protein expression. In particular, the MF-NPs could induce the expression of EGFR targeting chimeric antigen receptors (EGFR-CARs) on the NK cell surface, which improved the cells' anti-cancer cytotoxic effect both in vitro and in vivo. Finally, when NK cells labeled with MF-NPs were injected into live mice, MF-NP–labeled NK cells could be successfully imaged using fluorescence and MR imaging devices. Our findings indicate that MF-NPs have great potential for application of NK cells, as well as other types of cell therapies involving genetic engineering and in vivo monitoring of cell trafficking. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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