Cellular uptake mechanism and intracellular fate of hydrophobically modified glycol chitosan nanoparticles

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 necessar...

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Veröffentlicht in:Journal of controlled release 2009-05, Vol.135 (3), p.259-267
Hauptverfasser: Nam, Hae Yun, Kwon, Seok Min, Chung, Hyunjin, Lee, Seung-Young, Kwon, Seung-Hae, Jeon, Hyesung, Kim, Yoonkyung, Park, Jae Hyung, Kim, Joon, Her, Songwook, Oh, Yu-Kyoung, Kwon, Ick Chan, Kim, Kwangmeyung, Jeong, Seo Young
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container_end_page 267
container_issue 3
container_start_page 259
container_title Journal of controlled release
container_volume 135
creator Nam, Hae Yun
Kwon, Seok Min
Chung, Hyunjin
Lee, Seung-Young
Kwon, Seung-Hae
Jeon, Hyesung
Kim, Yoonkyung
Park, Jae Hyung
Kim, Joon
Her, Songwook
Oh, Yu-Kyoung
Kwon, Ick Chan
Kim, Kwangmeyung
Jeong, Seo Young
description 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. 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. [Display omitted]
doi_str_mv 10.1016/j.jconrel.2009.01.018
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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. 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. 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subjects Biological and medical sciences
Carbocyanines - metabolism
Cells - metabolism
Chitosan - chemistry
Drug Carriers - chemistry
Drug Carriers - pharmacology
Drug delivery system
Endocytosis
Endocytosis - drug effects
Fluorescent Dyes - metabolism
General pharmacology
HeLa Cells
Humans
Hydrophobic and Hydrophilic Interactions
Hydrophobically modified glycol chitosan
Intracellular trafficking
Medical sciences
Nanoparticles - chemistry
Nanoparticles - ultrastructure
Nanostructures - chemistry
Nanostructures - ultrastructure
Particle Size
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Self-assembled nanoparticles
title Cellular uptake mechanism and intracellular fate of hydrophobically modified glycol chitosan nanoparticles
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