한빛사 논문
Kwang-Soo Kima,1, Jun-Hyeok Hana,b,1, Jung-Hoon Parkc, Hyung-Keun Kima, Seung Hee Choia, Gyeong Ryeong Kima, Haengseok Songa, Hee Jung And, Dong Keun Hana,*, Wooram Parka,*, Kyung-Soon Parka,*
a Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam, Gyeonggi 13488, Republic of Korea
b College of Life Sciences Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
c Biomedical Engineering Research Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
d Department of Pathology, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam, Gyeonggi 13496, Republic of Korea
*Corresponding authors
1These authors equally contributed to this work.
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.
Keywords : Gene therapy; Drug delivery; Nanoparticles; Adoptive immunotherapy (AIT); Natural killer (NK) cells; Cell tracking
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