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
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2014
·
IF 3.432
Miao-Miao Xun,Yan-Hong Liu,Qian Guo,Ji Zhang,Qin-Fang Zhang,Wan-Xia Wu,Xiao-Qi Yu
Routine clinical implementation of human gene therapy requires safe and efficient gene delivery methods. Linear biodegradable polyesters with carbon–carbon double bonds are prepared from unsaturated diacids and diols . Subsequent appending of low molecular weight PEI by Michael addition gives target cationic polymers efficiently. Agarose gel retardation and fluorescence quenching assays show that these materials have good DNA binding ability and can completely retard plasmid DNA at weight ratio of 0.8. The formed polyplexes have appropriate sizes around 275 nm and zeta-potential values about +20–35 mV. The cytotoxicities of these polymers assayed by MTT are much lower than that of 25 kDa PEI. In vitro transfection toward 7402, HEK293 and U-2OS cells show that polymer P1 may give dramatically higher transfection efficiency (TE) than 25 kDa PEI, especially in U-2OS cells, suggesting that such polymer might be promising non-viral gene vectors .
研究领域:
生物材料学
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基因治疗
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 3
·期 5
·911-918
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IF 0
Yuhua Song,Tingbin Zhang,Xiaoyan Song,Ling Zhang,Chunqiu Zhang,Jinfeng Xing,Xing-Jie Liang
The low transfection efficiency of polycations is still a major problem for successful gene therapy. To address this issue, in this study, hydrophilic poly(vinyl pyrrolidone)-graft-poly[2-(N,N-dimethylamino)ethyl methacrylate] (PVP-g-PDMAEMA) and amphiphilic poly(vinyl pyrrolidone)-graft-poly[2-(N,N-dimethylamino)ethyl methacrylate]-block-poly(methylmethacrylate) (PVP-g-PDMAEMA-b-PMMA) were synthesized via the atom transfer radical polymerization (ATRP) method, and their properties as gene vectors were investigated subsequently. PVP-g-PDMAEMA formed random coils in water and PVP-g-PDMAEMA-b-PMMA self-assembled into spherical core–shell micelles with a very low critical micelle concentration of only 6.3 × 10−3 mg mL−1. PVP-g-PDMAEMA-b-PMMA/pDNA polyplexes demonstrated an excellent gene transfection efficiency, which showed not only much higher gene transfection efficiency than PVP-g-PDMAEMA/pDNA polyplexes, but obviously surpassed 25k PEI at low N/P ratio around 3 on 293T cell lines. Hence, the results suggested that PVP-g-PDMAEMA-b-PMMA could be a highly efficient gene vector.
研究领域:
生物化学
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基因治疗
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材料科学
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DOI
PubMed
ACS Applied Bio Materials
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2021
·
IF 0
Hui-Zhen Yang,Ji Zhang,Yu Guo,Lin Pu,Xiao-Qi Yu
Nonviral gene vectors with stimulus responsiveness and self-reporting properties have broad application prospects in gene therapy. Herein, we developed a nanosized reduction-responsive cationic liposomal vector formed from DNS(Zn), in which a naphthalimide–sulfonamide group was used as the glutathione (GSH)-responsive group to generate a blue fluorescence signal at 458 nm. Macrocyclic polyamine (cyclen) was used as a cationic headgroup to facilitate Zn(II) coordination, which may reduce the cytotoxicity and improve transfection efficiency. The Zn-free and nonresponsive analogues were used for comparison. Fluorescent assays revealed that the GSH response of DNS(Zn) could increase the blue fluorescence signal and improve the DNA release in cells. The title material also showed higher positive ζ-potential than its nonresponsive analogue, resulting in stronger DNA binding ability and better cellular uptake. These advantages made DNS(Zn) a good candidate for nonviral gene delivery, and the transfection efficiency in HeLa cells was distinctly higher than that of its analogue and the commercially available transfection reagent. Besides plasmid DNA, DNS(Zn) could also deliver small interfering RNA (siRNA) with good gene silencing efficiency, extending the application of the liposomes. These results suggest that DNS(Zn) can serve as a highly efficient nucleic acid delivery vector with reduction-responsive fluorescence self-reporting ability in tumor cells.
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
✓ 已验证
产品关联
DOI
PubMed
ADVANCED FUNCTIONAL MATERIALS
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2020
·Vol. 30
·期 45
·2004783
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IF 16.836
Dongli Wang,Jie Song,Jing Wang,Zhiyi Zhang,Qing Shen,Jun Wang,Haiyan Guo,Ruifeng Wang,Cao Xie,Weiyue Lu,Min Liu
Low transfection efficacy of non-viral gene vectors restricts their applications. In this paper, N 1 ,N 3 -dicarbamimidoyl-5-methylisophthalamide (BGG) is designed as a functional group, in which two guanidyls are located at the meta positions of an aryl ring. BGG is conjugated with PAMAM G5 (G5-BGG) and G5-BGG/DNA complex is dispersed into a polyvinyl alcohol (PVA) hydrogel for local injection. Molecular docking, NMR, IR and Isothermal titration calorimetry (ITC) experiments demonstrate that G5-BGG has multiple molecular interactions with nucleic acids, which yield high binding affinity toward nucleic acids. Interestingly, the in vitro transfection efficiency and serum stability of G5-BGG are significantly improved when the BGG modification ratio is just one. The integrated G5-BGG/DNA complex is released from a PVA hydrogel sustainably, crosses the cell membrane and escapes from endosome/lysosome. After local injection only once, these features of the G5-BGG/DNA-loaded PVA hydrogel are found to improve antitumor efficiency in vivo, and antitumor efficiency is significantly better than PEI 25K. The results confirm that BGG is a potential group for developing non-viral gene vectors with high transfection efficacy.
研究领域:
遗传学
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药学
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生物医学工程
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产品关联
DOI
高影响因子
Polymers
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2018
·Vol. 10
·期 10
·1080
·
IF 2.935
Ju-Hui Zhang,Hui-Zhen Yang,Ji Zhang,Yan-Hong Liu,Xi He,Ya-Ping Xiao,Xiao-Qi Yu
The linking and modification of low molecular weight cationic polymers (oligomers) has become an attracted strategy to construct non-viral gene carriers with good transfection efficiency and much reduced cytotoxicity. In this study, PEI 600 Da was linked by biodegradable bridges containing rigid aromatic rings. The introduction of aromatic rings enhanced the DNA-binding ability of the target polymers and also improved the stability of the formed polymer/DNA complexes. The biodegradable property and resulted DNA release were verified by enzyme stimulated gel electrophoresis experiment. These materials have lower molecular weights compared to PEI 25 kDa, but exhibited higher transfection efficiency, especially in the presence of serum. Flow cytometry and confocal laser scanning microscopy results indicate that the polymers with aromatic rings could induce higher cellular uptake. This strategy for the construction of non-viral gene vectors may be applied as an efficient and promising method for gene delivery.Keywords:non-viral vectors;gene delivery;polyethylenimine;structure–activity relationship
研究领域:
遗传学
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生物技术
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药学
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产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
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2024
·Vol. 35
·期 41
·415102
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IF 2.9
Fang Kou,Wei Wang,Xiaohong Zhu,Tian-Yan Han,Yajun Shi,Bang-Le Zhang
The rise of gene therapy has solved many diseases that cannot be effectively treated by conventional methods. Gene vectors is very important to protect and deliver the therapeutic genes to the target site. Polyethyleneimine (PEI) modified with mannitol could enhance the gene transfection efficiency reported by our group previously. In order to further control and improve the effective gene release to action site, disulfide bonds were introduced into mannitol-modified PEI to construct new non-viral gene vectors PeiSM. The degrees of mannitol linking with disulfide bonds were screened. Among them, moderate mannitol-modified PEI with disulfide bonds showed the best transfection efficiency, and significantly enhanced long-term systemic transgene expression for 72 h in vivo even at a single dose administration, and could promote caveolae-mediated uptake through up-regulating the phosphorylation of caveolin-1 and increase the loaded gene release from the nanocomplexes in high glutathione intracellular environment. This functionalized gene delivery system can be used as an potential and safe non-viral nanovector for further gene therapy.
研究领域:
基因治疗
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药学
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2018
·
IF 4.37
Menghao Shi,Xiufeng Zhao,Jiulong Zhang,Shuang Pan,Chunrong Yang,Ying Wei,Haiyang Hu,Mingxi Qiao,Dawei Chen,Xiuli Zhao
Introduction Specific polo-like kinase (PLK1) silencing with small interface RNA (siRNA) may be an effective approach for PLK1-overexpressed lung cancer. However, low siRNA concentration into cytoplasm of tumor tissue severely limits its application. Materials and methods In this study, a novel triblock copolymer methoxy poly(ethylene glycol)-poly(histidine)-poly(sulfadimethoxine) (mPEG-PHis-PSD, shorten as PHD) was synthesized and used to construct novel nonviral gene vector with cationic liposomes. Results The resulting hybrid nanoparticles (PHD/LR) loaded with siPLK1 possessed excellent physiochemical properties. In vitro study indicated that PHD/LR could be efficiently internalized into human lung adenocarcinoma A549 cells and downregulated PLK1 protein expression to induce cell apoptosis, which was attributed to pH-induced instantaneous dissociation, efficient endo/lysosomal escape arose from PHD copolymer. Furthermore, in vivo antitumor activity demonstrated that PHD/LR could efficiently accumulated into tumor tissue and silenced PLK1 expression to possess antitumor activity. Conclusion Taken all these together, PHD/LR was expected to be a suitable carrier for specific delivering siRNA for lung cancer therapy.
研究领域:
癌症研究
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纳米技术
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药学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2021
·
IF 5.875
Guoxin Tan,Jiayang Li,Dandan Liu,Hao Pan,Renfang Zhu,Yue Yang,Weisan Pan
Gene therapy is a promising approach to many diseases, however, the barriers in the gene delivery restrict its application. Therefore, in the present study, an efficient non-viral gene vector (PRHF/N/D) for overcoming the barriers in gene delivery was prepared. The synthesized PRHF integrated the advantages of PAMAM and amino acids, which could improve the cellular uptake, enhance the endosomal escape ability and minimize cytotoxicity. To further enhance nuclear entry of carrier, the nuclear localization signal (NLS) peptide was selected to add in the PRHF/D polyplexes. The PRHF/N/D polyplexes demonstrated good condensation capacity, wonderful pDNA protection and low toxicity. Moreover, the PRHF/N/D polyplexes showed the excellent transfection efficiency than P/D. PRHF/N/D further improve transfection capability than PRHF/D in the presence of NLS. After 4 h of incubation, the mean fluorescence intensity of PRHF/N/D was also higher than the P/D and PRHF/D complexes. We then investigated the intracellular dissociation, the DNA is able to disassemble from PRHF/N/D gene carriers. Taken together, we exhibited that this PRHF/N/D polyplexes has the potential for use in the gene delivery.
研究领域:
药剂学
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分子生物学
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基因治疗
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2015
·
IF 7.705
Tian-Yuan Zhang,Bing Huang,Hai-Bin Wu,Jia-He Wu,Li-Ming Li,Yan-Xin Li,Yu-Lan Hu,Min Han,You-Qing Shen,Yasuhiko Tabata,Jian-Qing Gao
The success of conventional suicide gene therapy for cancer treatment is still limited because of lack of efficient delivery methods, as well as poor penetration into tumor tissues. Mesenchymal stem cells (MSCs) have recently emerged as potential vehicles in improving delivery issues. However, these stem cells are usually genetically modified using viral gene vectors for suicide gene overexpression to induce sufficient therapeutic efficacy. This approach may result in safety risks for clinical translation. Therefore, we designed a novel strategy that uses non-viral gene vector in modifying MSCs with suicide genes to reduce risks. In addition, these cells were co-administrated with prodrug-encapsulated liposomes for synergistic anti-tumor effects. Results demonstrate that this strategy is effective for gene and prodrug delivery, which co-target tumor tissues, to achieve a significant decrease in tumor colonization and a subsequent increase in survival in a murine melanoma lung metastasis model. Moreover, for the first time, we demonstrated the permeability of MSCs within tumor nests by using an in vitro 3D tumor spheroid model. Thus, the present study provides a new strategy to improve the delivery problem in conventional suicide gene therapy and enhance the therapeutic efficacy. Furthermore, this study also presents new findings to improve our understanding of MSCs in tumor-targeted gene delivery.
研究领域:
癌症生物学
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基因治疗
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干细胞研究
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药物科学
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肿瘤生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR CHEMISTRY AND PHYSICS
·
2015
·Vol. 216
·期 14
·1507-1515
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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
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分子生物学
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药剂学
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基因治疗
✓ 已验证
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
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药学
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生物技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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