상위피인용논문
- 조회2,982
한국과학기술연구원(KIST)
Abstract
Hae Yun Nama, e, 1, Seok Min Kwona, b, 1, Hyunjin Chunga, b, Seung-Young Leea, Seung-Hae Kwonc, Hyesung Jeona, Yoonkyung Kima, Jae Hyung Parkd, e, Joon Kimb, Songwook Herc, Yu-Kyoung Ohb, Ick Chan Kwona, Kwangmeyung Kima, Seo Young Jeonge
a Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea
b School of Life Science and Biotechnology, Korea University, 1 Anam-dong, Seongbuk-gu, Seoul 136-701, South Korea
c Division of Analytical Bio-imaging, Chuncheon Center, Korea Basic Science Institute, 192-1, Hyoja2-dong, Chuncheon, Gangwon-do, 200-701, South Korea
d Department of Advanced Polymer and Fiber Materials, College of Environment and Applied Chemistry, Kyung Hee University, Gyeonggi-do 449-710, South Korea
e Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, South Korea
Corresponding authors. Kim is to be contacted at Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
Jeong, Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, South Korea.
1These authors contributed equally to this paper.
Abstract
Polymeric nanoparticle-based carriers are promising agents for the targeted delivery of therapeutics to the intracellular site of action. To optimize the efficacy in delivery, often the tuning of physicochemical properties (i.e., particle size, shape, surface charge, lipophilicity, etc.) is necessary, in a manner specific to each type of nanoparticle. Recent studies showed an efficient tumor targeting by hydrophobically modified glycol chitosan (HGC) nanoparticles through the enhanced permeability and retention (EPR) effect. As a continued effort, here the investigations on the cellular uptake mechanism and the intracellular fate of the HGC nanoparticles are reported. The HGC nanoparticle, prepared by a partial derivatization of the free amino groups of glycol chitosan (GC) with 5β-cholanic acid, had a globular shape with the average diameter of 359 nm and the zeta potential of ca. 22 mV. Interestingly, these nanoparticles showed an enhanced distribution in the whole cells, compared to the parent hydrophilic GC polymers. In vitro experiments with endocytic inhibitors suggested that several distinct uptake pathways (e.g., clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis) are involved in the internalization of HGC. Some HGC nanoparticles were found entrapped in the lysosomes upon entry, as determined by TEM and colocalization studies. Given such favorable properties including low toxicity, biocompatibility, and fast uptake by several nondestructive endocytic pathways, our HGC nanoparticles may serve as a versatile carrier for the intracellular delivery of therapeutic agents.
Graphical abstract
The cellular uptake profile of HGC was time-and dose-dependent. Pre-treatment of HeLa cells with several endocytic inhibitors (e.g., chlorpromazine, filipin III, and amiloride) indicated that more than one mechanism is involved simultaneously in the HGC nanoparticles' uptake.
Keywords: Hydrophobically modified glycol chitosan; Self-assembled nanoparticles; Intracellular trafficking; Endocytosis; Drug delivery system
논문정보
- Research article
- 2009년 05월 (BRIC 등록일 )
- 국내 연구진
- 의약학 > 약학
- 60회 이상 인용된 논문
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