EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2018
·
IF 4.816
Ya-Ping Xiao,Ji Zhang,Yan-Hong Liu,Ju-Hui Zhang,Qing-Ying Yu,Zheng Huang,Xiao-Qi Yu
Fluorinated biomaterials have been reported to have promising features as non-viral gene carriers. In this study, a series of fluorinated polymeric gene carriers were synthesized via Michael addition from low molecular weight polyethyleneimine (PEI) and fluorobenzoic acids (FBAs)-based linking compounds with different numbers of fluorine atoms . The structure-activity relationship (SAR) of these materials was systematically investigated. SAR studies showed that fluorine could screen the positive charge of these polymers. However, this shielding effect of fluorine would endow fluorinated polymers with good balance between DNA condensation and release. In vitro transfection results suggested that these fluorinated polymers could mediate efficient gene delivery. Flow cytometry and confocal microscopy studies demonstrated that more efficient cell uptake could be achieved by fluorinated materials with more fluorine atoms. Cytotoxicity assays showed that these fluorinated materials exhibited very low cytotoxicity even at high mass ratios. This study demonstrates that FBA-based fluorinated biopolymers have the potential for practical application.
研究领域:
生物材料学
·
基因治疗
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
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
·
基因治疗
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYMER
·
2015
·
IF 3.562
Miao-Miao Xun,Ya-Ping Xiao,Ji Zhang,Yan-Hong Liu,Qi Peng,Qian Guo,Wan-Xia Wu,Yong Xu,Xiao-Qi Yu
A series of polycationic gene delivery vectors were synthesized via Michael addition from low molecular weight PEI and linking compounds with various heteroatom compositions . Agarose gel electrophoresis results reveal that these polymers can well condense plasmid DNA and can protect DNA from degradation by nuclease. The formed polyplexes , which are stable toward serum, have uniform spherical nanoparticles with appropriate sizes around 200–350 nm and zeta-potentials about +40 mV. In vitro experiments show that these polymers have lower cytotoxicity and higher transfection efficiency than 25 KDa PEI. Furthermore, the title materials exhibit excellent serum tolerance. With the present of 10% serum, up to 19 times higher transfection efficiency than PEI was obtained, and no obvious decrease of TE was observed even the serum concentration was raised to >40%. Flow cytometry and confocal microscopy studies also demonstrate the good serum tolerance of the materials.
研究领域:
生物化学
·
分子生物学
·
基因治疗
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 13
·2660-2670
·
IF 4.726
Qian Guo,Yan-Hong Liu,Miao-Miao Xun,Ji Zhang,Zheng Huang,Xue-Dong Zhou,Xiao-Qi Yu
A series of cationic polymers (P1–P5) were designed and synthesized using a ring-opening polymerization strategy based on low molecular weight polyethyleneimine (PEI) and using diglycidyl ethers as the bridging moiety. Although these polymers have reduced amino group density relative to 25 kDa PEI, their pH buffering capacity and deoxyribonucleic acid (DNA) binding ability were seldom affected. They were able to condense plasmid DNA (pDNA) well to form nanoparticles of suitable sizes (150–300 nm) and positive zeta potentials (+25–40 mV). Cell Counting Kit-8 (CCK-8) assays revealed that polyplexes formed from these polymers have lower cytotoxicity than those derived from PEI. Luciferase reporter gene delivery experiments indicated that these polymers have much better transfection efficiency than 25 kDa PEI, especially P2 and P5. Unlike PEI, serum has little negative effect on the transfection by these materials, and their transfection efficiencies were seldom reduced even with high concentrations of serum. Under optimized conditions, up to 400 times higher transfection efficiency than with PEI could be achieved. Several assays including gel electrophoresis, dynamic light scattering and transmission electron microscopy also confirmed the good serum tolerance of these polyplexes. The evenly distributed hydroxyl groups formed by the ring-opening polymerization are considered to contribute much to their high serum tolerance, and such polymerization might be a promising strategy for the design of efficient non-viral gene delivery vectors.
研究领域:
生物化学
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基因治疗
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材料科学
✓ 已验证
DOI
PubMed
高影响因子
ORGANIC & BIOMOLECULAR CHEMISTRY
·
2012
·Vol. 11
·期 7
·1242-1250
·
IF 3.696
Miao-Miao Xun,Xue-Chao Zhang,Ji Zhang,Qian-Qian Jiang,Wen-Jing Yi,Wen Zhu,Xiao-Qi Yu
Non-viral gene vectors play an important role in the development of gene therapy. In this report, different hydrophobic chains were introduced into low molecular weight (LMW) PEI-based biodegradable oligomers to form a series of lipopolymers (LPs), and their structure–activity relationships were studied. Results revealed that the nine polymers can condense plasmid DNA well to form nanoparticles with appropriate sizes (120–250 nm) and positive zeta-potentials (+25–40 V). In vitro experiments were carried out and it was found that LP2 showed much higher transfection efficiency both in the presence and in the absence of serum under the polymer/DNA weight ratio of 0.8 in A549 cells.
研究领域:
生物技术
·
基因治疗
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）