CARBOHYDRATE POLYMERS
·
2014
·
IF 3.916
Jingfen Han,Jia Cai,Wuyinga Borjihan,Tsogzolmaa Ganbold,Tariq M. Rana,Huricha Baigude
RNA interference (RNAi) down-regulates gene expression post-transcriptionally, which is a therapeutically significant phenomenon that could potentially reduce the level of disease related proteins that are undruggable by conventional small molecular approaches. However, clinical application of small interference RNAs (siRNAs) requires design of potent siRNA sequences and development of safe and efficient delivery systems. To create a biocompatible siRNA delivery agent, we chemically modified natural polysaccharide curdlan in a regioselective manner to introduce amino group in the glucose units. The resulting 6-amino-curdlan (6AC) is water soluble and forms nanoparticles upon complexing with siRNAs. The novel curdlan-based nanoparticles efficiently delivered siRNAs to human cancer cells and mouse primary cells, and reduced 70–90% of target mRNA level. Moreover, 6AC nanoparticles delivered siRNA targeting eGFP to mouse embryonic stem (mES) cells stably expressing eGFP, and produced substantial reductions of GFP protein level. The novel curdlan-based nanoparticle is a promising vehicle for delivery of short RNAs to knock down endogenous mRNAs.
研究领域:
生物技术
·
分子生物学
·
药物递送
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Tsogzolmaa Ganbold,Shuqin Han,Agula Hasi,Huricha Baigude
Natural carbohydrate polymer-based nanoparticles have great biocompatibility that is required for the safe delivery of various drugs including nucleic acid therapeutics. Herein, we designed curdlan-based nanoparticles for cancer cell targeted delivery of short interfering RNA (siRNA). iRGD peptide conjugated 6-amino-6-deoxy curdlan specifically delivered siRNA to integrin expressing cancer cells. Incubation of cancer cells with free iRGD peptide competitively blocked cellular uptake of the iRGD functionalized curdlan nanoparticles. Chloroquine but not nystatin inhibited cellular uptake of iRGD functionalized curdlan nanoparticles, indicating that the iRGD peptide conjugated curdlan nanoparticles were internalized through the receptor (clathrin)-mediated endocytosis. Moreover, a disease related gene Plk1 was substantially knocked down by siRNA carried by 6AC-iRGD nanoparticles in HepG2 cells. Our data suggested that iRGD functionalized curdlan may provide a biocompatible carrier for siRNA delivery.
研究领域:
生物医学工程
·
分子生物学
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2017
·
IF 4.811
Yao Tong,Tsogzolmaa Ganbold,Huricha Baigude
Cationic polymers are powerful carriers for intracellular delivery of therapeutic nucleic acids. However, the positively charged macromolecules have considerable cytotoxicity and often induce irreversible damages to the cells and tissues, which greatly negate the clinical application of such materials as drug delivery system. Herein, we report the synthesis of novel amphoteric polymers based on curdlan, and the evaluation of their cytotoxicity as well as the nucleic acid delivery efficiency. β-(1,3)-polyglucuronic acid, a TEMPO-oxidized derivative of curdlan, was chemically modified by conjugation of tetraethylenepentamine. The resulting amphoteric polymers, denoted tetraethylenepentamine-curdlan (TEPAC) polymers have the degree of substitution (DS) ranging from 25% to 48%. The result of MTT assay indicated that TEPAC polymers have negligible cytotoxicity on HeLa cells and A549 cells. The novel amphoteric polymers efficiently bound with plasmid DNA and delivered pcDNA-eGFP plasmid to 293T cells and induced expression of GFP 48 h after the transfection. Moreover, TEPAC polymers delivered siRNA to HeLa cells and HepG2 cells in high efficiency, and induced significant RNAi for the expression of an endogenous gene. Collectively, our data demonstrate that the novel curdlan-based amphoteric polymers are biocompatible and may provide a highly efficient system for the delivery of therapeutic nucleic acids.
研究领域:
生物材料学
·
分子生物学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Wenmei Hu,Xindong Xu,Xingyan Wang,Tinghong Ma,Yuting Li,Xianglin Qin,Jibin Wei,Shan Chen
This study investigated the influence of curdlan on the gel properties of whey protein isolate (WPI). Results demonstrated that curdlan significantly improved the water-holding capacity, gel strength and rheological properties of the WPI gels. Moreover, it promoted the unfolding of the molecular structures of WPI, which was manifested by the transition from α-helix to β-sheet, an increase in free sulfhydryl content and a decrease in surface hydrophobicity. Furthermore, 4 % curdlan promoted the formation of WPI with uniform and compact elastic gel network structures, primarily attributed to disulphide bonds, hydrogen bonds and hydrophobic interactions. However, when the addition of curdlan exceeds 4 %, excessive entanglement of curdlan chains and steric hindrance effects hinder the unfolding and folding of protein structures, weaken their interaction, result in a loose network structure and affect the gel properties. In conclusion, this study demonstrates that curdlan can effectively improve the gelling properties of WPI, suggesting its potential application in low-calorie gel-based dairy products.
研究领域:
食品科学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Qingming Bao,Mingming Bao,Hai Xiao,Tsogzolmaa Ganbold,Shuqin Han,Huricha Baigude
The simultaneous delivery of CpG oligonucleotide along with short interfering RNA (siRNA) has the potential to significantly boost the anticancer impact of siRNA medications. Our previous research demonstrated that Curdlan nanoparticles functionalized with adenosine are capable of selectively delivering therapeutic siRNA to cancerous cells through endocytosis mediated by adenosine receptors. Herein, we synthesized a dual-ligand-functionalized Curdlan polymer (denoted by CuMAN) to simultaneously target tumor cells and tumor-associated macrophages (TAMs). CuMAN nanoparticles containing CpG and siRNA demonstrated enhanced uptake by B16F10 tumor cells and bone marrow-derived macrophages, which are facilitated by AR on tumor cells and mannose receptor on macrophages. This led to increased release of pro-inflammatory cytokines in both in vitro and in vivo settings. The synergistic effect of CpG on TAMs and RNAi on tumor cells mediated by the CuMAN nanoparticle not only suppressed the tumor growth but also strongly inhibited the lung metastasis. Our findings indicate that the CuMAN nanoparticle has potential as an effective dual-targeting delivery system for nucleic acid therapeutics.
研究领域:
生物医学工程
·
肿瘤免疫学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Zhixiang Cai,Hongbin Zhang
The chain conformational change in curdlan during carboxymethylation was investigated using nuclear magnetic resonance (NMR), circular dichroism (CD) spectroscopy, and atomic force microscopy (AFM). The distributions of carboxymethyl substituents within anhydroglucose unit (AGU) of CMCD were found to follow the order of OH (6) > OH (4) > OH (2) for CMCD with a low DS and OH (6) > OH (2) > OH (4) for CMCD with relatively high DS. The increased carboxymethylation level induced the chain conformation transition of curdlan from triple helix to random coil in water. The DS of 0.25 was the critical value of chain conformation transition, below which CMCD chains were triple helices. For DS larger than 0.25, CMCD existed in the state of random coils. The intermolecular hydrogen bonding between C2 hydroxyls in AGU sustained the triple helical conformation and stiffness of the polymer chain, which weakened with the increase in DS.
研究领域:
生物化学
·
高分子科学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Yinga Wu,Jia Cai,Jingfen Han,Huricha Baigude
Tissue-specific delivery of therapeutic RNAi has great potential for clinical applications. Receptor-mediated endocytosis plays a crucial role in targeted delivery of biotherapeutics including short interfering RNA (siRNA). Previously we reported a novel Curdlan-based nanoparticle for intracellular delivery of siRNA. Here we designed a nanoparticle based on ligand-functionalized Curdlan. Disaccharides were site-specifically conjugated to 6-deoxy-6-amino Curdlan, and the cell line specificity, cellular uptake, cytotoxicity, and siRNA delivery efficiency of the corresponding disaccharide-modified 6-deoxy-6-amino-Curdlan were investigated. Observation by fluorescence microscopy as well as flow cytometry showed that galactose-containing Curdlan derivatives delivered fluorescently labeled short nucleic acid to HepG2 cells expressing ASGPR receptor but not in other cells lacking surface ASGPR protein. Moreover, highly galactose-substituted Curdlan derivatives delivered siRNA specifically to ASGPR-expressing cells and induced RNAi activities, silencing endogenous GAPDH gene expression. Our data demonstrated that galactose-functionalized 6-deoxy-6-amino-Curdlan is a promising carrier for short therapeutic nucleic acids for clinical applications.
研究领域:
生物技术
·
分子生物学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2018
·
IF 5.158
Rong Tang,Jie Hao,Ruijie Zong,Fangxia Wu,Yangyang Zeng,Zhenqing Zhang
In this study, the TEMPO-mediated (TEMPO/NaBr/NaClO) oxidation pattern of curdlan was investigated through comprehensively structural analysis of the corresponding oxidized products. During the structural analysis, infrared spectroscopy (IR), nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography tandem multiple angle laser scattering (GPC-MALS) and ultra-high performance liquid chromatography tandem quadrupole time of flight mass spectrometry (UHPLC-Q/TOF-MS) were applied. As a result, the homogenous β1-3 polyglucuronic acids (MW, 49.8, 29.8 and 7.0 kDa) were obtained with proper amount of oxidant (5.36 mmol NaClO) at various temperatures (4, 25, 50 °C), respectively. Compared to the oxidation of 1–4 linked glucan (starch and cellulose) with TEMPO-mediated system at same reaction conditions, higher degree of specific oxidation and less degradation were observed in that of 1–3 linked curdlan. The glycosylation at position 3 could stabilize the sugar ring, which inactivates the non-specific oxidation related hydroxyl groups on the sugar ring. Thus, the TEMPO-mediated system has higher selectivity to oxidize the primary hydroxyl groups of 1–3 linked curdlan and form polyglucuronic acid than those observed in the oxidation of starch and cellulose. In addition, same as those observed in previous work about starch, higher the temperature was used in the oxidation with TEMPO system, higher the activity of oxidant (NaClO solution) was, more non-specific oxidation occurred, and more the degradation were observed.
研究领域:
生物化学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2021
·
IF 3.517
Muqier Muqier,Hai Xiao,Xiang Yu,Yifeng Li,Mingming Bao,Qingming Bao,Shuqin Han,Huricha Baigude
Cationic polysaccharides have shown excellent ability of nucleic acids delivery. However, cationic curdlan derivatives with high degree of amination cause damage to the cell membrane and induce considerable cytotoxicity, limiting their in vivo application. Herein, we synthesized PEGylated 6-amino-6-deoxy-curdlan derivatives containing cleavable disulfide bonds. The resulting polymers (denote 6AC-2S PEGx) not only showed high affinity to siRNA but also exhibited significantly decreased cytotoxicity and hemolysis effect, while showing remarkable in vitro transfection efficiency. In vivo study demonstrated that 6AC-2S PEG40, which had a lower LD50 value than that of 6AC-100, did not cause liver damage, as the i.v. injection of 6AC-2S PEG40 to mouse did not increase serum level of ALT/AST. Furthermore, tissue distribution results showed that 6AC-2S PEG40 successfully delivered siRNA to liver, lung and spleen. Collectively, our data confirmed that PEGylation can increase the biocompatibility of cationic curdlan derivatives, which is a promising carrier for nucleic acid therapeutics.
研究领域:
药学
·
生物技术
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Ali Mohsin,Waqas Qamar Zaman,Meijin Guo,Waheed Ahmed,Imran Mahmood Khan,Sobia Niazi,Abdur Rehman,Haifeng Hang,Yingping Zhuang
In this study, we prepared a series of edible blend films of xanthan and curdlan by mixing different ratios of these two biopolymers . Characterization techniques like FTIR, XRD, TGA and SEM analysis were applied to investigate the newly formed films. Moreover, mechanical properties, moisture absorbance properties and water solubility of these films were also determined. The obtained results demonstrated that the strong intermolecular hydrogen bonding was observed between xanthan and curdlan at pH 5. At this pH, the xanthan-curdlan hydrogel retained the original structure of xanthan and sustained self-aggregation of xanthan chains via hydrogen bonding, which led to strong intermolecular bonding between xanthan and curdlan. Furthermore, the 5:5 and 4:6 ratios of xanthan and curdlan showed greater interaction in the blend films that resulted in their excellent miscibility. Moreover, highest tensile strength of 28.13 and 26.45 MPa were also found in the same rational of XG/CG blend films. In addition, it was observed that the curdlan incorporation improved the water solubility properties of XG/CG blend films. Conclusively, this xanthan/curdlan nexus with excellent mechanical and moisture barrier properties confirm its potential application and prospective use as food packaging material.
研究领域:
食品科学
·
材料科学
·
生物化学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Lei Luo,Qing Zhou,Yingkui Hu,Qiang Ding,Zongbao Zhou,Chuang Wang,Xiaoying Wang,Hang Li,Shunqing Tang
The immunostimulatory activity of polysaccharides can improve human immunity, but their activity is low and prompting the activity is a great challenge. Curdlan, is a linear beta-1,3-glucan and has the potential to induce immune responses. However, owing to its tight triple helix structure and insolubility in water, its immunostimulatory activity is weakened. The keyway to promote its immunostimulatory activity is to relax its tight triple helix structure. In this work, methoxypolyethylene glycol (mPEG) was grafted onto curdlan (curdlan- g -mPEG) to unwind its triple helix structure. With its grafting mPEG, the water solubility of curdlan was enhanced. Moreover, with curdlan- g -mPEG treatment, macrophages secreted more tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 and exhibited favorable phagocytosis of bacteria ( Staphylococcus aureus and Pseudomonas aeruginosa ). These results reveal that curdlan- g -mPEG as an immunostimulant has potential applications in immunology and antibiotics.
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2026
·Vol. 9
·期 17
·8100-8114
·
IF 5.6
Lu Dongxue,Xiao Tian,Jiang Lu,Xu Yuge,Wang Yumeng,Guo Tengfei,Yang Ru,Wang Yifei,Wu Chaoxi
Polysaccharide-based hydrogels with strong tissue adhesion, injectability, and self-healing capability are highly desirable for wound management, yet their performance is often limited by rigid polymer conformations and insufficient interfacial interactions. Here, we report a mussel-inspired, dopamine-grafted curdlan hydrogel (Cur-DA) featuring a predominantly single-helical β-glucan architecture. Cur-DA hydrogels were synthesized under alkaline conditions using ethylene glycol diglycidyl ether (EGDE) as a linker, thereby facilitating regioselective dopamine grafting at the C6 position of curdlan. Spectroscopic analyses (UV–Vis, FTIR, solid-state 13 C NMR, XRD, and circular dichroism), together with XPS characterization, confirmed successful dopamine incorporation and a conformational transition from native triple helices to more flexible single helices. With this single-helical architecture and catechol functionalization, Cur-DA formed a nanofibrous, porous network with high water content (>90%), increased swelling capacity, and excellent mechanical compliance. Owing to catechol-mediated interfacial interactions and the mobility of single-helical chains, which likely serve as dynamic “sticky ends,” Cur-DA hydrogels exhibited robust tissue adhesion (up to 10.21 kPa), self-healing, and outstanding injectability. In vitro assays indicated excellent hemocompatibility and cytocompatibility. In a murine full-thickness skin wound model, an optimized formulation (Cur-DA3) accelerated wound closure, promoted re-epithelialization, and enhanced collagen deposition without inducing systemic toxicity. This work establishes a conformation-engineering strategy for β-glucan hydrogels and highlights Cur-DA as a promising injectable, adhesive wound dressing.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）