A Polysaccharide Carrier for Immunostimulatory CpG DNAs To Enhance Cytokine Secretion

Mizu, Masami; Koumoto, Kazuya; Anada, Takahisa; Matsumoto, Takahiro; Numata, Munenori; Shinkai, Seiji; Nagasaki, Takeshi; Sakurai, Kazuo

doi:10.1021/ja031978+

Cited by 56 publications

(43 citation statements)

References 16 publications

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“…In many studies including our preceding work, cationic functional groups or cell-fusion peptides were attached to carriers to enhance cellular uptake (9,10). Although these chemical modifications enhanced the cytokine secretion dramatically, they could not have targetability at all.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Cytokine Secretion from Primary Macrophages due to Dectin-1 Mediated Uptake of CpG DNA/β-1,3-Glucan Complex

et al. 2010

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Unmethylated CpG sequences (CpG DNA) can induce Th1 response and thus become a potential immunotherapeutic agent. A key step in the treatment is to transport CpG DNA to its receptor TLR9 located in the endocytosis pathway of target immune cells. For the effective transport, we prepared a novel complex from a β-1,3-glucan schizophyllan (SPG) and CpG DNA, and administered the complex to murine peritoneal macrophages that had been previously activated by thioglycollate and expressed a major β-1,3-glucan receptor Dectin-1 on the cellular surface. Flow cytometric analysis and microscopic observation showed that the complex was taken up by the macrophage through Dectin-1 mediated pathway. Indeed, ELISA demonstrated that IL-12 production was increased sigmoidally with increasing SPG/CpG DNA ratio in the complexation, and reached the maximum at the SPG-rich composition. In the present work, we describe a new approach to deliver CpG DNA to immune cells by use of a β-1,3-glucan/DNA complex.

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Section: Introductionmentioning

confidence: 99%

Enhanced Cytokine Secretion from Primary Macrophages due to Dectin-1 Mediated Uptake of CpG DNA/β-1,3-Glucan Complex

et al. 2010

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“…[64][65][66] In this method, the -1,3-glucan main chain remains intact and thus able to complex with ODNs. The first step oxidizes SPG with NaIO 4 to yield formyl groups that are only generated in the side chain, because this oxidation specifically cleave 1,2-diol.…”

Section: Application Of the Complex To An Odn Delivery Vehiclementioning

confidence: 99%

A Novel Polysaccharide/Polynucleotide Complex and its Application to Bio-functional DNA Delivery System

Mochizuki

Sakurai

2009

Polym. J.

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-1,3-glucans such as schizophyllan (SPG) and curdlan can form a novel complex with polynucleotides through hydrogen bonding between the two main chain glucoses and the one nucleotide base. The complex can be used as carriers for therapeutically functional polynucleotides such as antisense DNA, siRNA and CpG ODN. Cellular uptake efficiency of the complexes was remarkably enhanced by attaching functional groups that can be recognized by cells. Recent immunology revealed that a receptor dectin-1, normally expressed on antigen presenting cells (APCs) such as macrophages and dendritic cells, can recognize -1,3-glucans. This fact suggests that the complex can deliver the bound DNA to the APCs. The present article reviews the fundamental and structural studies of this novel complex as well as a recent result for applying its complex to DNA carriers.

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“…30 Other leading cationic polysaccharides that have been investigated as gene vectors include dextran, 7,[31][32][33] pullulan, 34,35 pectin, 36 and schizophyllan. 22,37 The cationization of polysaccharide is a promising strategy to develop nonviral gene vectors for use in gene therapy. 38,39 Polysaccharides represent a structurally diverse class of macromolecules of widespread occurrence in nature and offer a high capacity for carrying biological information because they have great potential for structural variability.…”

Section: Introductionmentioning

confidence: 99%

Delivery of a transforming growth factor β-1 plasmid to mesenchymal stem cells via cationized Pleurotus eryngii polysaccharide nanoparticles

Deng

Cao²,

Wang³

et al. 2012

IJN

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Abstract:The objective of this study was to investigate the use of cationized Pleurotus eryngii polysaccharide (CPEPS) as a nonviral gene delivery vehicle to transfer plasmid DNA encoding transforming growth factor beta-1 (pTGF-β1) into mesenchymal stem cells (MSCs) in vitro. Crude P. eryngii polysaccharide was purified, and then cationized by grafting spermine onto the backbone of the polysaccharide. Agarose gel electrophoresis, transmission electron microscopy, and a Nano Sense Zetasizer (Malvern Instruments, Malvern, UK) were used to characterize the CPEPS-pTGF-β1 nanoparticles. The findings of cytotoxicity analysis showed that when the nanoparticles were formulated with a CPEPS/pTGF-β1 weight ratio $ 10:1, a greater gel retardation effect was observed during agarose gel electrophoresis. The CPEPS-pTGF-β1 nanoparticles with a weight ratio of 20:1, respectively, possessed an average particle size of 80.8 nm in diameter and a zeta potential of +17.4 ± 0.1 mV. Significantly, these CPEPS-pTGF-β1 nanoparticles showed lower cytotoxicity and higher transfection efficiency than both polyethylenimine (25 kDa) (P = 0.006, Student's t-test) and Lipofectamine TM 2000(P = 0.002, Student's t-test). Additionally, the messenger RNA expression level of TGF-β1 in MSCs transfected with CPEPS-pTGF-β1 nanoparticles was significantly higher than that of free plasmid DNA-transfected MSCs and slightly elevated compared with that of Lipofectamine 2000-transfected MSCs. Flow cytometry analysis demonstrated that 92.38% of MSCs were arrested in the G1 phase after being transfected with CPEPS-pTGF-β1 nanoparticles, indicating a tendency toward differentiation. In summary, the findings of this study suggest that the CPEPS-pTGF-β1 nanoparticles prepared in this work exhibited excellent transfection efficiency and low toxicity. Therefore, they could be developed into a promising nonviral vector for gene delivery in vitro.

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A Polysaccharide Carrier for Immunostimulatory CpG DNAs To Enhance Cytokine Secretion

Cited by 56 publications

References 16 publications

Enhanced Cytokine Secretion from Primary Macrophages due to Dectin-1 Mediated Uptake of CpG DNA/β-1,3-Glucan Complex

Enhanced Cytokine Secretion from Primary Macrophages due to Dectin-1 Mediated Uptake of CpG DNA/β-1,3-Glucan Complex

A Novel Polysaccharide/Polynucleotide Complex and its Application to Bio-functional DNA Delivery System

Delivery of a transforming growth factor β-1 plasmid to mesenchymal stem cells via cationized Pleurotus eryngii polysaccharide nanoparticles

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A Polysaccharide Carrier for Immunostimulatory CpG DNAs To Enhance Cytokine Secretion

Cited by 56 publications

References 16 publications

Enhanced Cytokine Secretion from Primary Macrophages due to Dectin-1 Mediated Uptake of CpG DNA/β-1,3-Glucan Complex

Enhanced Cytokine Secretion from Primary Macrophages due to Dectin-1 Mediated Uptake of CpG DNA/β-1,3-Glucan Complex

A Novel Polysaccharide/Polynucleotide Complex and its Application to Bio-functional DNA Delivery System

Delivery of a transforming growth factor &beta;-1 plasmid to mesenchymal stem cells via cationized Pleurotus eryngii polysaccharide nanoparticles

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Delivery of a transforming growth factor β-1 plasmid to mesenchymal stem cells via cationized Pleurotus eryngii polysaccharide nanoparticles