pH-Responsive PEGylated nanogels as targetable and low invasive endosomolytic agents to induce the enhanced transfection efficiency of nonviral gene vectors |
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Authors: | Motoi Oishi Hisato Hayashi Keiji Itaka Kazunori Kataoka Yukio Nagasaki |
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Institution: | (1) Tsukuba Research Center for Interdisciplinary Materials Science (TIMS), University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki 305-8573, Japan;(2) Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki 305-8573, Japan;(3) Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;(4) Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan |
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Abstract: | A pH-responsive PEGylated nanogel was successfully prepared by means of emulsion copolymerization of 2-(N,N-diethylamino)ethyl methacrylate (AMA) with heterobifunctional poly(ethylene glycol) (PEG) bearing a 4-vinylbenzyl group at
the α-end and a lactose moiety at the ω-end in the presence of potassium persulfate and ethyleneglycol dimethacrylate as a
cross-linker. Polyplex micelle composed of PEG-block-poly(l-lysine) copolymer and plasmid DNA (PEG-b-PLL/pDNA) exhibited a far more efficient transfection ability in the presence of lac-nanogel-8k-1.0% (PEG, M
n = 8000; cross-linking density, 1.0%) than the PEG-b-PLL/pDNA polyplex micelle alone (in the absence of lac-nanogel-8k-1.0%), suggesting that an appreciable fraction of lac-nanogel-8k-1.0%
along with the PEG-b-PLL/pDNA polyplex micelle is taken up into the HuH-7 cells through the asialoglycoprotein receptor-mediated endocytosis process
mediated by the cluster of a large number of lactose moieties on the surface of lac-nanogel-8k-1.0%, followed by the effective
disruption of the endosome by the buffer effect of the unprotonated PAMA core in lac-nanogel-8k-1.0%.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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Keywords: | Core-shell type nanogel pH-sensitive volume phase transition Endosomolytic agent Gene vector PEG-tethering surface |
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