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Open AccessArticle

Preparation of Biodegradable Oligo(lactide)s-Grafted Dextran Nanogels for Efficient Drug Delivery by Controlling Intracellular Traffic

1
Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35 Yamate, Suita, Osaka 564-8680, Japan
2
Organization for Research and Development of Innovative Science and Technology (ORDIST), Kansai University, 3-3-35 Yamate, Suita, Osaka 564-8680, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(6), 1606; https://doi.org/10.3390/ijms19061606
Received: 13 April 2018 / Revised: 19 May 2018 / Accepted: 27 May 2018 / Published: 30 May 2018
(This article belongs to the Special Issue Smart Polymers for Biomedical Applications)
Nanogels, nanometer-sized hydrogel particles, have great potential as drug delivery carriers. To achieve effective drug delivery to the active sites in a cell, control of intracellular traffic is important. In this study, we prepared nanogels composed of dextran with oligolactide (OLA) chains attached via disulfide bonds (Dex-g-SS-OLA) that collapse under the reductive conditions of the cytosol to achieve efficient drug delivery. In addition, we introduced galactose (Gal) residues on the nanogels, to enhance cellular uptake by receptor-mediated endocytosis, and secondary oligo-amine (tetraethylenepentamine) groups, to aid in escape from endosomes via proton sponge effects. The obtained Dex-g-SS-OLA with attached Gal residues and tetraethylenepentamine (EI4) groups, EI4/Gal-Dex-g-SS-OLA, formed a nanogel with a hydrodynamic diameter of ca. 203 nm in phosphate-buffered solution. The collapse of the EI4/Gal-Dex-g-SS-OLA nanogels under reductive conditions was confirmed by a decrease in the hydrodynamic diameter in the presence of reductive agents. The specific uptake of the hydrogels into HepG2 cells and their intercellular behavior were investigated by flow cytometry and confocal laser scanning microscopy using fluorescence dye-labeled nanogels. Escape from the endosome and subsequent collapse in the cytosol of the EI4/Gal-Dex-g-SS-OLA were observed. These biodegradable nanogels that collapse under reductive conditions in the cytosol should have great potential as efficient drug carriers in, for example, cancer chemotherapy. View Full-Text
Keywords: biodegradable nanogel; disulfide bond; drug delivery; cellular traffic biodegradable nanogel; disulfide bond; drug delivery; cellular traffic
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MDPI and ACS Style

Ohya, Y.; Takahashi, A.; Kuzuya, A. Preparation of Biodegradable Oligo(lactide)s-Grafted Dextran Nanogels for Efficient Drug Delivery by Controlling Intracellular Traffic. Int. J. Mol. Sci. 2018, 19, 1606.

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