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

Hae Yun Nam, Seok Min Kwon, Hyunjin Chung, Seung Young Lee, Seung Hae Kwon, Hyesung Jeon, Yoonkyung Kim, Jae Hyung Park, Joon Kim, Songwook Her, Yu Kyoung Oh, Ick Chan Kwon, Kwangmeyung Kim, Seo Young Jeong

Research output: Contribution to journalArticlepeer-review

519 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)259-267
Number of pages9
JournalJournal of Controlled Release
Issue number3
Publication statusPublished - 2009 May 5

Bibliographical note

Funding Information:
This research was financially supported by the Real-Time Molecular Imaging Project and Global Research Laboratory Program of MEST and by the Korea Research Foundation Grant funded by the Korea Government (MOEHRD, Basic Research Promotion Fund) (KRF-2007-412-J00304), and by a grant (08162KFDA550) from Korea Food & Drug Administration in 2008. We thank Dr. Kyung Eun Lee at Korea University for obtaining TEM images of our samples.


  • Drug delivery system
  • Endocytosis
  • Hydrophobically modified glycol chitosan
  • Intracellular trafficking
  • Self-assembled nanoparticles

ASJC Scopus subject areas

  • Pharmaceutical Science


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