Nam, Hae Yun Kwon, Seok Min Chung, Hyunjin Lee, Seung-Young Kwon, Seung-Hae Jeon, Hyesung Kim, Ybonkyung Park, Jae Hyung Kim, Joon Her, Songwook Oh, Yu-Kyoung Kwon, Ick Chan Kim, Kwangmeyung Jeong, Seo Young 2024-01-20T21:31:26Z 2024-01-20T21:31:26Z 2021-09-03 2009-05-05 0168-3659 https://pubs.kist.re.kr/handle/201004/132494 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 5 beta-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 macro pinocytosis) 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. (c) 2009 Elsevier B.V. All rights reserved. English ELSEVIER SCIENCE BV SELF-ASSEMBLED NANOPARTICLES DRUG-DELIVERY COATED PIT PATHWAYS CARRIERS PROTEIN ACID TRAFFICKING TRANSPORT RELEASE Cellular uptake mechanism and intracellular fate of hydrophobically modified glycol chitosan nanoparticles Article 10.1016/j.jconrel.2009.01.018 1 JOURNAL OF CONTROLLED RELEASE, v.135, no.3, pp.259 - 267 JOURNAL OF CONTROLLED RELEASE 135 3 259 267 scie scopus 000265702200011 2-s2.0-63649092083 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article SELF-ASSEMBLED NANOPARTICLES DRUG-DELIVERY COATED PIT PATHWAYS CARRIERS PROTEIN ACID TRAFFICKING TRANSPORT RELEASE Hydrophobically modified glycol chitosan Self-assembled nanoparticles Intracellular trafficking Endocytosis Drug delivery system