A novel gene carrier prepared from triple helical β-glucan and polydeoxyadenylic acid

Liu, Qingye; Wang, Chaoqun; Chen, Yan; Xu, Xiaojuan; Zhang, Lina

doi:10.1039/c3tb21195a

Cited by 32 publications

(19 citation statements)

References 55 publications

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“…Moreover, when single polydeoxyadenylic acid (poly(dA)) chains are added during the reassembling process of s‐LNT, two s‐LNT chains are able to selectively combine a poly(dA) chain via hydrogen bonding to form a novel triple helical hybrid (denoted s‐LNT/poly(dA)) with high thermal stability under the physiological condition, effectively protecting poly(dA) from degradation. Based on these findings, we have established a promising gene delivering vehicle based on the s‐LNT/poly(dA) nanocomposite, in which an immune gene of CpG DNA was linked with a poly(dA) tail through a disulfide bond to stimulate IL‐12p40 and IL‐6 secretion in RAW264.7 cells with no cytotoxicity . It seems that LNT is a potential carrier delivering genes to the target sites with good safety in vivo.…”

Section: Introductionmentioning

confidence: 75%

Orally Delivered Antisense Oligodeoxyribonucleotides of TNF‐α via Polysaccharide‐Based Nanocomposites Targeting Intestinal Inflammation

Duan

Sun

et al. 2019

Adv Healthcare Materials

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has been regarded as an alternative strategy to treat IBD by downregulating TNF-α levels produced by the activated macrophages. [17][18][19][20] However, the success of RNAi has to mainly rely on the gene carriers to protect the target genes. Many researchers have been working on the discovery of drug and gene carriers with high efficiency and biocompatibility. [21][22][23][24][25] Electrostatic condensation of macromolecular genes into nanoparticles by cationic carriers has been acknowledged to be a common strategy for the nonviral delivery. [26][27][28] As reported, polycations acting as gene carriers possess such limitation as lack of superior biocompatibility, insufficient release of delivered genes, easy absorption, and quick elimination in the bloodstream. [29][30][31][32] Therefore, developing new delivery strategies is necessitated to substantially overcome these shortcomings for promoting application of RNAi technology.Polysaccharides such as schizophyllan, curdlan, yeast glucan, lentinan, and auricularian have been introduced as soft matrices to accommodate inorganic nanoparticles, fluorescent dyes, drugs, and oligonucleotides for versatile therapeutic functions due to their unique structural characteristics. [33] Of these, lentinan (LNT for short) has been demonstrated to exist as a triple helix (denoted t-LNT) in water and as a single flexible chain (denoted s-LNT) under such conditions as in dimethyl sulfoxide (DMSO), [34,35] in aqueous sodium hydroxide (NaOH) solution with the NaOH concentration higher than 0.08 m, [36] and in water at the temperature of higher than 135 °C. [37] When the DMSO content decreases gradually through adding water or dialysis against water, the s-LNT chains reassemble into the triple helix (denoted r-LNT) owing to the hydrophobic and hydrogen bonding interactions. [38] Moreover, when single polydeoxyadenylic acid (poly(dA)) chains are added during the reassembling process of s-LNT, two s-LNT chains are able to selectively combine a poly(dA) chain via hydrogen bonding to form a novel triple helical hybrid (denoted s-LNT/ poly(dA)) with high thermal stability under the physiological condition, [39] effectively protecting poly(dA) from degradation. Based on these findings, we have established a promising gene delivering vehicle based on the s-LNT/poly(dA) nanocomposite, in which an immune gene of CpG DNA was linked with a poly(dA) tail through a disulfide bond to stimulate IL-12p40 Tumor necrosis factor alpha (TNF-α) is usually regarded as a potential target for inflammatory bowel disease therapy. Herein, a promising strategy for effective delivery of phosphorothioated antisense oligodeoxyribonucleotide of TNF-α (PS-ATNF-α), targeting the intestinal inflammation based on the interaction of the single chain of triple helical β-glucan (s-LNT) with polydeoxyadenylic acid [poly(dA)], and the colon-specific degradation of chitosanalginate (CA) hydrogel, is reported. The target gene of PS-ATNF-α, with a poly(dA) tail through a disulfide bond (-SS-), interacts with s-LNT to form a r...

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Section: Introductionmentioning

confidence: 75%

Orally Delivered Antisense Oligodeoxyribonucleotides of TNF‐α via Polysaccharide‐Based Nanocomposites Targeting Intestinal Inflammation

Duan

Sun

et al. 2019

Adv Healthcare Materials

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“…It has been reported that β-glucans from yeast, fungi, grain and seaweed adopt the pathogen associated molecular pattern (PAMP), so that they can trigger specific recognition and internalization by some cells [ 18 ]. To clarify whether LNT was recognized or internalized by MCF-7 cells, LNT was conjugated with FITC (denoted FITC-LNT) and incubated with MCF-7 cells at 4°C, followed by a confocal microscopy observation.…”

Section: Resultsmentioning

confidence: 99%

The β-glucan fromLentinus edodessuppresses cell proliferation and promotes apoptosis in estrogen receptor positive breast cancers

Zou

2017

Oncotarget

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Breast cancer is now the most common cancer in worldwide women, and novel interventions are needed to overcome the resistance occurring in the estrogen-targeted endocrine therapy. Herein, we demonstrate that the β-glucan from Lentinus edodes (LNT) exhibited a profound inhibition ratio of ∼53% against estrogen receptor positive (ER+) MCF-7 tumor growth in nude mice similar to the positive control of cisplatin. Immunohistochemistry images showed that LNT evidently suppressed cell proliferation and promoted apoptosis in MCF-7 tumor tissues. The Western blotting analysis indicated that LNT up-regulated the tumor suppressor p53, phosphorylated extracellular signal-regulated kinase1/2 (p-ERK1/2), cleaved-Caspase 3 and poly [ADP (ribose)] polymerase 1 (PARP 1) protein levels, and reduced the expression of mouse double minute 2 (MDM2), telomerase reverse transcriptase (TERT), nuclear factor-kappa B (NF-κB) p65, B-cell lymphoma-2 (Bcl-2), estrogen receptor α (ERα), etc. in tumor tissues. Moreover, LNT significantly suppressed phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt) and mammalian target of rapamycin (mTOR) protein levels. It was thus proposed that LNT inhibited MCF-7 tumor growth through suppressing cell proliferation and enhancing apoptosis possibly via multiple pathways such as PI3K/Akt/mTOR, NF-κB-, ERK-, ERα-, caspase- and p53-dependent pathways. Interestingly, the cell viability assay, siRNA transfection, Western blotting and flow cytometric analysis suggested that LNT targeted p53/ERα to only suppress cell proliferation via cell cycle arrest at G2/M phase without apoptosis in vitro. The big difference between in vivo and in vitro data suggested that the immune responses triggered by the polysaccharide should mainly contribute to the apoptotic effect in vivo. Overall, this work provides a novel strategy to treat ER+ breast cancers by using a naturally occurring β-glucan from mushrooms.

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“…Due to their unique physicochemical properties and biological activities, the polysaccharides have been widely investigated and used (Jia et al 2013;Li et al 2014;Liu et al 2014;Luan et al 2011;Xu et al 2012;Yu et al 2014b). In addition to decolorization of brown chitooligomers by ozonation, ozone will play an important role on the research and application of the polysaccharides.…”

Section: Discussionmentioning

confidence: 99%

Decolorization of Brown Chitooligomers in Aqueous Solution by Ozonation

Zhang

Xie

et al. 2015

Ozone: Science & Engineering

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Brown chitooligomers were obtained by gamma irradiation. Decolorization of brown chitooligomers in aqueous solution by ozonation was investigated. It was found that ozone could decolorize the brown chitooligomers in aqueous solution.When the pH value was below 2.93, the ozone treatment could inhibit yellowing and browning of chitooligomers in aqueous solution. As a result, the chitooligomers were slightly depolymerized by ozonation. The characterization showed that the decolorization by ozonation did not lead to the significant modification of chemical structure of the chitooligomers.

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A novel gene carrier prepared from triple helical β-glucan and polydeoxyadenylic acid

Cited by 32 publications

References 55 publications

Orally Delivered Antisense Oligodeoxyribonucleotides of TNF‐α via Polysaccharide‐Based Nanocomposites Targeting Intestinal Inflammation

Orally Delivered Antisense Oligodeoxyribonucleotides of TNF‐α via Polysaccharide‐Based Nanocomposites Targeting Intestinal Inflammation

The β-glucan fromLentinus edodessuppresses cell proliferation and promotes apoptosis in estrogen receptor positive breast cancers

Decolorization of Brown Chitooligomers in Aqueous Solution by Ozonation

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