Cellular Uptake Mechanism and Intracellular Fate of Hydrophobically Modified Glycol Chitosan Nanoparticles

Title
Cellular Uptake Mechanism and Intracellular Fate of Hydrophobically Modified Glycol Chitosan Nanoparticles
Authors
남혜윤권석민정현진이승영권승해전혜성김윤경박재형김준허송욱오유경권익찬김광명정서영
Issue Date
2009-05
Publisher
Journal of controlled release : official journal of the Controlled Release Society
Citation
VOL 135, NO 3, 259-267
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.
URI
http://pubs.kist.re.kr/handle/201004/36081
ISSN
0168-3659
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KIST Publication > Article
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