Hepatocyte-Selective Gene Transfer by Galactosylated Protein/Linear Polyethyleneimine/Plasmid DNA Complexes in Mice

Hohokabe, Miyuki; Higuchi, Yuriko; Mukai, Hidefumi; Kawakami, Shigeru; Hashida, Mitsuru

doi:10.1166/jbn.2007.034

Cited by 6 publications

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“…Of these, the release of pDNA from endosomes/lysosomes into the cytoplasm after internalization is a major obstacle for efficient gene expression in hepatocytes. Therefore, manipulation of this process by functional peptides or the use of PEI with pH buffering functions in lysosomes [53] by galactosylated macromolecules might allow high transfection rates in vivo [40,49,[54][55][56]. Our group developed a mannosylated macromolecular carrier system for cell-selective targeting based on dextran, which has high solubility, an abundance of hydroxyl groups for chemical modification, low immunogenicity, and is used in the clinic as a plasma expander [2].…”

Section: Glycosylated Macromolecules For Cell-selective Targetingmentioning

confidence: 99%

Glycosylation-mediated targeting of carriers

Kawakami

Hashida

2014

Journal of Controlled Release

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For safe and effective therapy, drugs should be delivered selectively to their target tissues or cells at an optimal rate. Drug delivery system technology maximizes the therapeutic efficacy and minimizes unfavorable drug actions by controlling their distribution profiles. Ligand-receptor binding is a typical example of specific recognition mechanisms in the body; therefore, ligand-modified drug carriers have been developed for active targeting based on receptor-mediated endocytosis. Among the various ligands reported thus far, sugar recognition is a promising approach for active targeting because of their high affinity and expression. Glycosylation has been applied for both macromolecular and liposomal carriers for cell-selective drug targeting.Recently, the combination of ultrasound exposure and glycosylated bubble liposomes has been developed. In this review, recent advances of glycosylation-mediated targeted drug delivery systems are discussed.

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Section: Glycosylated Macromolecules For Cell-selective Targetingmentioning

confidence: 99%

Glycosylation-mediated targeting of carriers

Kawakami

Hashida

2014

Journal of Controlled Release

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Asialoglycoprotein receptor mediated hepatocyte targeting — Strategies and applications

D’Souza

Devarajan

2015

Journal of Controlled Release

421

291

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Immunostimulatory Characteristics Induced by Linear Polyethyleneimine–Plasmid DNA Complexes in Cultured Macrophages

et al. 2009

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Intravenously injected plasmid DNA (pDNA) complexed with cationic liposome (lipoplexes) caused NF-kappaB-mediated cytokine production from macrophages, induced by CpG sequence in the pDNA. We have reported that cytokine production caused by linear polyethyleneimine (PEI)-pDNA complexes (PEI polyplexes) was much lower than that caused by lipoplexes (Kawakami, S., Ito, Y., Charoensit, P., Yamashita, F., and Hashida, M. [2006]. J. Pharmacol. Exp. Ther. 317, 1382-1390). As Toll-like receptor-9 recognizing CpG sequence is expressed in the endosomal compartment, we hypothesized that the buffering capacity of PEI enhanced the escape of PEI polyplexes from endosomes, and that consequently cytokine production was decreased. In this study, the mechanism of lower cytokine production induced by PEI polyplexes, compared with lipoplexes, was investigated using the murine macrophage-like cell line RAW 264.7. Although transfection efficacy and cellular association were similar for PEI polyplexes and lipoplexes, tumor necrosis factor-alpha and interleukin-6 production and NF-kappaB activation caused by polyplexes were significantly lower than with lipoplexes. As for intracellular distribution, PEI polyplexes spread into cytosol whereas lipoplexes accumulated in vesicles, suggesting enhancement of escape from endosomes by PEI. Bafilomycin A1, an inhibitor of early endosomes, enhanced cytokine production and NF-kappaB activation by PEI polyplexes but not by lipoplexes; however, chloroquine, an inhibitor of late endosomes, inhibited PEI polyplex-induced cytokine production and NF-kappaB activation, suggesting that the buffering effect of PEI on early endosomes decreases NF-kappaB-mediated cytokine production. In conclusion, we demonstrate that cytokine production and NF-kappaB activation induced by PEI polyplexes are significantly lower than with lipoplexes in cultured macrophages. The significantly low cytokine response of PEI polyplexes may be due to effective transition of PEI polyplexes from endosomes to cytosol.

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Hepatocyte-Selective Gene Transfer by Galactosylated Protein/Linear Polyethyleneimine/Plasmid DNA Complexes in Mice

Cited by 6 publications

References 0 publications

Glycosylation-mediated targeting of carriers

Glycosylation-mediated targeting of carriers

Asialoglycoprotein receptor mediated hepatocyte targeting — Strategies and applications

Immunostimulatory Characteristics Induced by Linear Polyethyleneimine–Plasmid DNA Complexes in Cultured Macrophages

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