JOURNAL OF MATERIALS CHEMISTRY
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2011
·Vol. 21
·期 38
·14639-14645
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IF 5.101
Xiao-Jun Cai,Hai-Qing Dong,Wen-Juan Xia,Hui-Yun Wen,Xue-Quan Li,Jin-Hai Yu,Yong-Yong Li,Dong-Lu Shi
Engineered PEG-detachable catiomers were developed as non-viral gene vectors to detach the PEG layers responsive to the intracellular reducing environment. These catiomers were found to exhibit high DNA binding ability and reduced cytotoxicity, as evidenced in agarose gel electrophoresis and MTT assays. The size of the mPEG-SS-PLL/DNA complexes was around 100 nm with a regular spherical shape, as observed under transmission electron microscopy (TEM). The complexes were stably dispersed in an aqueous medium with 10% serum. However, fast aggregation was observed in the presence of 10 mM glutathione (GSH) due to detachment of the PEG segment via disulfide cleavage. These complexes showed high transfection efficiency in 293T and Hela cells under optimized conditions. The experimental results indicated that the mPEG-SS-PLL catiomers may have promising potential as a non-viral gene vector.
研究领域:
生物化学
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分子生物学
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基因治疗
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DOI
高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 3
·期 1
·119-126
·
IF 0
Yinan Zhao,Shubiao Zhang,Yuan Zhang,Shaohui Cui,Huiying Chen,Defu Zhi,Yuhong Zhen,Shufen Zhang,Leaf Huang
Several novel tri-peptide cationic lipids were designed and synthesized for delivering DNA and siRNA. They have tri-lysine and tri-ornithine as headgroups, a carbamate group as a linker and 12 and 14 carbon atom alkyl groups as tails. These tri-peptide cationic lipids were prepared into cationic liposomes for the study of the physicochemical properties and gene delivery. Their particle size, zeta potential and DNA-binding were characterized to show that they were suitable for gene transfection. Further results indicate that these lipids can transfer DNA and siRNA very efficiently into NCI-H460 and Hep-2 tumor cells. The selected lipid, CDO14, was able to deliver combined siRNAs against c-Myc and VEGF for silencing distinct oncogenic pathways in lung tumors of mice, with little in vitro and in vivo toxicity.
研究领域:
药学
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分子生物学
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癌症研究
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DOI
PubMed
ACS Applied Bio Materials
·
2020
·
IF 0
Bo Wang,Jian Huang,Mengling Zhang,Yun Wang,Huibo Wang,Yurong Ma,Xiaodong Zhao,Xiao Wang,Changhong Liu,Hui Huang,Yang Liu,Fang Lu,Hengxiu Yu,Mingwang Shao,Zhenhui Kang
Genetic engineering is an important technology in plant sciences. The current delivery techniques, such as Agrobacterium-mediated gene transfer and gene gun instant gene expression system, always need a very complicated process or have host-range limitations due to the inhibition of the cell wall structure. Here, we demonstrate that a nanocomposite (CDP) prepared by combining polyethyleneimine (PEI) with carbon dot (CD) was confirmed as a good vector for gene transfection in both animal and plant cells, especially in intact plants. Efficient DNA delivery and strong gene expression without DNA integration are accomplished in rice (Oryza Sativa japonica), wheat (Triticum aestivum), and mung bean (Phaseolus radiatus) leaves and rice roots. Notably, the CDP successfully deliver the hydamycin resistance gene into the rice and induce hygromycin resistance in rice. Also, CDP can achieve the β-glucuronidase gene delivery and expression in mature rice embryo induced callus. The CDP not only facilitates plasmid transport into cells but also protects DNA from DNase degradation. Our work provides a highly efficient DNA delivery system for instant gene expression, which could be a useful and fast gene engineering tool for functional research in plant biology.
研究领域:
植物科学
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基因工程
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纳米技术
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DOI
PubMed
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
·
2019
·Vol. 83
·期 4
·622-632
·
IF 1.297
Song Xiaowei,Yan Guanghai,Quan Songshi,Jin Enhao,Quan Jishan,Jin Guangyu
To noninvasively monitor the effect of gene therapy and achieve an optimal therapeutic effect, liposomes encapsulated polyethylenimine (PEI)-coated superparamagnetic iron oxide nanoparticles (SPION) with dual functions of MRI diagnosis and gene therapy were prepared. SPION was synthesized via co-precipitation, and then modified with PEI via thiourea reaction. The liposomes encapsulating PEI-SPION (LP-PEI-SPION) were prepared by ethanol injection. Fourier transform infrared spectra confirmed that PEI was successfully modified onto SPION, and thermogravimetric analysis indicated that the PEI content was about 17.1%. The LP-PEI-SPION/DNA had a small particle size of 253.07 ± 0.90 nm. LP-PEI-SPION/DNA had low cytotoxicity with more than 80% of the cell survival rates and high transfection efficiency compared with Lipofectamine® 2000/DNA. Additionally, it also showed good MRI effect on three cell lines. The liposomes encapsulating PEI-SPION (lipopolyplexes) have been successfully prepared as MRI contrast agents and gene delivery vectors, which may have great theoretical research significance and clinical potentials.Abbreviations: PEI, polyethylenimine; SPION, superparamagnetic iron oxide nanoparticles; LP-PEI-SPION, liposomes encapsulating PEI-SPION; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; ICP-MS, inductively coupled plasma mass spectrometry; XRD, X-ray diffraction; TEM, transmission electron microscope; TGA, thermogravimetric analysis; DOTAP, 1,2-dioleoyl-3-trimethylammonium-propane; DOPE, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; Chol, cholesterol.
研究领域:
生物医学工程
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纳米技术
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基因治疗
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分子生物学
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医学成像
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Yu Zou,Quan Zhou,Yinan Zhao,Defu Zhi,Huiying Chen,Rui Wang,Benzhi Ju,Shubiao Zhang
Ionizable lipids are the leading vectors for gene therapy. Understanding the effects of molecular structure on efficient gene delivery is one of the most important challenges for maximizing the utility of such lipid vectors. We synthesized an array of pH-responsive and ionizable lipids to investigate the relationship between lipid structure and activity. The optimized lipid (EDM) has double tertiary amines in the headgroup and an ester linker. EDM exhibited efficient DNA and siRNA delivery to, and gene silencing of, A549 cells. EDM has a p K a value of 6.67, which enabled it to quickly escape from the endosome after entering the cell; the ester linkages rapidly degraded and enabled gene release into the cytoplasm. EDM also delivered IGF-1R siRNA to inhibit tumor growth and induce cancer cell apoptosis by efficient inhibition of IGF-1R expression in mice. Our study on the structure–activity relationships of ionizable lipids will facilitate clinical applications.
研究领域:
药学
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基因治疗
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 11
·2275-2285
·
IF 5.344
Ya-Ping Xiao,Ji Zhang,Yan-Hong Liu,Zheng Huang,Yu Guo,Xiao-Qi Yu
Cationic polymers have shown great potential in the delivery of nucleic acids and proteins. In this study, a series of pyrimidine-based cationic polymers were synthesized via the Michael addition reaction from pyrimidine-based linkages and low molecular weight polyethyleneimine (PEI). The structure–activity relationship (SAR) of these materials in DNA and protein delivery was investigated. These materials could condense both DNA and protein into nanoparticles with proper sizes and zeta-potentials. In vitro experiments indicated that such polymers were efficient in transporting DNA and proteins into cells. Furthermore, the bioactivity of the genes and proteins encapsulated in these polymers were maintained during the delivery processes. Among the polymers, U-PEI600 synthesized from a uracil-containing linker and PEI 600 Da mediated comparable gene expression to PEI 25 kDa. Moreover, the activities of β-galactosidase delivered by U-PEI600 were well maintained after entering the cells. Evaluation using an immune response assay showed that the U-PEI600/OVA polyplex could stimulate greater production of immune factors with low cytotoxicity. Our study provides a strategy for the construction of cationic polymeric gene and cytosolic protein vectors with high efficiency and low toxicity.
研究领域:
生物材料
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基因治疗
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蛋白质工程
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纳米技术
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药剂学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2013
·Vol. 1
·期 46
·6418-6426
·
IF 0
Wenyu Li,Peng Zhang,Kun Zheng,Qiaoling Hu,Youxiang Wang
Extracellular stability to protect DNA against nucleases and stimulus-triggered intracellular DNA release are key factors in designing non-viral gene vectors. In this study, the diselenide-linked polycation mPEG–SeSe–PEI was developed as a new type of PEG-detachable gene vector for redox-responsive gene delivery. The corresponding stable analog mPEG–PEI and the disulfide-linked polycation mPEG–SS–PEI were synthesized as controls. The results showed that all the PEGylated polycations could condense DNA into tightly packed spherical nanoparticles about 80 nm in size, which showed excellent stability under physiological conditions. The results of zeta-potential measurements, stability tests and DNA release ability assay indicated that at a GSH concentration of 0.3 mM, the diselenide bonds were more easily cleaved than disulfide bonds, which facilitated dePEGylation and DNA release. Meanwhile, it was interestingly found that mPEG–SeSe–PEI/DNA polyplexes showed higher gene expression than mPEG–SS–PEI/DNA polyplexes in both HEK293T and HepG2 cells. Confocal laser scanning microscope (CLSM) images revealed that mPEG–SeSe–PEI/DNA polyplexes showed more efficient endosomal escape ability than mPEG–SS–PEI/DNA polyplexes. Based on these results, the diselenide bonds as a novel strategy are more suitable to address the challenging problem of extracellular stability and intracellular DNA release.
研究领域:
基因递送
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聚合物化学
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分子生物学
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生物医学工程
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DOI
PubMed
MACROMOLECULAR CHEMISTRY AND PHYSICS
·
2015
·Vol. 216
·期 14
·1507-1515
·
IF 2.616
Yunna Kong,Wenyu Li,Qianying Mao,Youxiang Wang
Supramolecular assembly provides a new strategy for designing various gene carriers for deoxyribonucleic acid (DNA) delivery. In this work, supramolecular pseudo-block conjugates based on star-shaped polycation are developed as novel nonviral gene vector. First, cyclodextrin (CD) is selected as core and grafted with low molecular weight polyethylenimine (PEI 1800 ) as arms to obtain high molecular weight star-shaped polycation CD-PEI 8 (SCP). Then, azobenzene (Az) modified poly(ethylene glycol) is synthesized and named as azobenzene modified poly(ethylene glycol) (Az-PEG). Subsequently, the supramolecular pseudo-block conjugates are prepared via host–guest interaction between CD and Az. The result suggests that SCP/Az-PEG condenses DNA into spherical nanoparticles with sizes of around 150 nm. The in vitro experiment shows that the cell viability of DNA/SCP/Az-PEG polyplexes is significantly improved compared with that of PEI 25k /DNA polyplexes. The PEGylation does not decrease the cellular uptake efficiency and transfection efficiency. Furthermore, the cellular trafficking shows that PEGylation does not significantly influence nuclear entry. The star-shaped architecture of polycation plays an important role in gene delivery.
研究领域:
生物医学工程
·
分子生物学
·
药剂学
·
基因治疗
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产品关联
DOI
高影响因子
Acta Biomaterialia
·
2020
·
IF 7.242
Yihang Wu,Ling Wang,Yue Xiong,Quanming Zhou,Linxian Li,Guanyu Chen,Yulei Ping,Gary Davidson,Pavel A. Levkin,Liqian Gao,Wenbin Deng
Development of non-viral gene vectors which can efficiently and safely transfect plasmid DNA and siRNA into cells is of great importance for gene therapy. Despite lots of efforts spent, it is still imperative to develop suitable gene vectors with better transfection efficiency and low cytotoxicity. To this end, we successfully designed, synthesized and screened a library of 120 polymers ( via nucleophilic substitution reaction between dihalides and amines). With cell-based transfection screening assays, 120 polymers were tested to evaluate their transfection efficiency of transporting DNA and siRNA into cells. Our results indicated that hydrophobic modification could greatly enhance cationic polymers’ transfection efficiency, and polymers with long linkers usually showed better transfection performance, especially for polymers with the linker of 1, 12-dibromododecane (L3 linker). Besides, polyalkylamines exhibited better transfection efficiency with the polymer particle size around 200 nm and the zeta potential in the range of + 40 mV to +50 mV. Interestingly, polymer particles made from N15HL3 not only exhibited better DNA transfection efficiency in HEK 293T cells but also showed higher siRNA transfection efficiency in U87 Luc-GFP cells together with low cell toxicity than Lipofectamine 2000 (one of commercial transfection reagents). Therefore, it is hoped that our study here not only provides promising gene vector candidates for further evaluation in gene therapy, but also provides valuable insights for better understanding of the relationship between the chemical structures and gene transfection efficiency to rationally design better non-viral gene vectors for gene therapy in the future.
研究领域:
基因治疗
·
药学
·
生物技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2014
·Vol. 5
·期 11
·8404-8414
·
IF 3.708
Yongbo Yang,Jinrui Wang,Xiaoda Li,Li Lin,Xiuli Yue
This paper reported the development of a multifunctional contrast agent for near infrared (NIR) fluorescent/ultrasonic bimodal imaging and gene delivery. CuInS2–ZnS alloyed quantum dots (ZCIS QDs) were coated with polyethyleneimine (PEI) to complex plasmid DNA (pDNA), followed by adsorption onto the surface of microbubbles (MBs) generated from the surfactant mixture of Span 60 and Tween 80. It was found that the obtained composite agent of MBs@QDs@PEI/pDNA had excellent capability to enhance both ultrasound and fluorescence imaging. In addition, an in vitro cell experiment showed that pDNA could be released from MBs@QDs@PEI/pDNA and internalized by target HeLa cells to realize a relatively high transfection efficiency by ultrasound-targeted microbubble destruction. Furthermore, the cytotoxicity, immune toxicity and histological evaluation showed that MBs@QDs@PEI/pDNA had a good biocompatibility for medical application. Therefore, such a multifunction agent could operate as a promising platform for targeting gene delivery under the guidance of NIR fluorescent/ultrasonic bimodal imaging.
研究领域:
医学影像
·
基因治疗
·
纳米技术
·
生物医学工程
✓ 已验证
DOI
高影响因子
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