10 results on '"Liu, Yan-Hong"'
Search Results
2. Low molecular weight PEI-appended polyesters as non-viral gene delivery vectors.
- Author
-
Xun, Miao-Miao, Liu, Yan-Hong, Guo, Qian, Zhang, Ji, Zhang, Qin-Fang, Wu, Wan-Xia, and Yu, Xiao-Qi
- Subjects
- *
MOLECULAR weights , *POLYESTERS , *VIRAL genes , *GENE delivery techniques , *GENETIC vectors , *MICHAEL reaction - Abstract
Abstract: 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. [Copyright &y& Elsevier]
- Published
- 2014
- Full Text
- View/download PDF
3. Amino Acid-Linked Low Molecular Weight Polyethylenimine for Improved Gene Delivery and Biocompatibility.
- Author
-
Wu, Xiao-Ru, Zhang, Ji, Zhang, Ju-Hui, Xiao, Ya-Ping, He, Xi, Liu, Yan-Hong, and Yu, Xiao-Qi
- Subjects
MOLECULAR weights ,POLYETHYLENEIMINE ,HISTIDINE ,GEL permeation chromatography ,GENES ,BIOCOMPATIBILITY ,GENE therapy - Abstract
The construction of efficient and low toxic non-viral gene delivery vectors is of great significance for gene therapy. Herein, two novel polycations were constructed via Michael addition from low molecular weight polyethylenimine (PEI) 600 Da and amino acid-containing linkages. Lysine and histidine were introduced for the purpose of improved DNA binding and pH buffering capacity, respectively. The ester bonds afforded the polymer biodegradability, which was confirmed by the gel permeation chromatography (GPC) measurement. The polymers could well condense DNA into nanoparticles and protect DNA from degradation by nuclease. Compared with PEI 25 kDa, these polymers showed higher transfection efficiency, lower toxicity, and better serum tolerance. Study of this mechanism revealed that the polyplexes enter the cells mainly through caveolae-mediated endocytosis pathway; this, together with their biodegradability, facilitates the internalization of polyplexes and the release of DNA. The results reveal that the amino acid-linked low molecular weight PEI polymers could serve as promising candidates for non-viral gene delivery. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
4. Biodegradable Gene Carriers Containing Rigid Aromatic Linkage with Enhanced DNA Binding and Cell Uptake.
- Author
-
Zhang, Ju-Hui, Yang, Hui-Zhen, Zhang, Ji, Liu, Yan-Hong, He, Xi, Xiao, Ya-Ping, and Yu, Xiao-Qi
- Subjects
BIODEGRADABLE materials ,CATIONIC polymers ,POLYMERS ,GENE delivery techniques ,GENE transfection ,OLIGOMERS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
5. Low molecular weight PEI-based fluorinated polymers for efficient gene delivery.
- Author
-
Xiao, Ya-Ping, Zhang, Ji, Liu, Yan-Hong, Zhang, Ju-Hui, Yu, Qing-Ying, Huang, Zheng, and Yu, Xiao-Qi
- Subjects
- *
MOLECULAR weights , *FLUORINATION , *GENE delivery techniques , *BIOMATERIALS , *MICHAEL reaction , *PHARMACEUTICAL chemistry - Abstract
Abstract 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. Graphical abstract Image 1 Highlights • Effect of fluorine atom number and location on gene delivery ability was investigated. • Fluorine atoms may facilitate DNA condensation and stabilize the polymer/DNA complex. • Fluorination of the polymeric gene vectors enhanced their transfection efficiency. • Fluorination improved uptake efficiency, and more fluorine atoms led to higher uptake. • All fluorinated polymeric vectors exhibited very low cytotoxicity even at high dosage. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
6. Fluorinated polymer emulsion systems: Construction and application in delivering genes and proteins.
- Author
-
Xiao, Ya-Ping, Zhang, Ji, Liu, Yan-Hong, Huang, Zheng, and Yu, Xiao-Qi
- Subjects
- *
FLUOROPOLYMERS , *GENE transfection , *EMULSIONS , *NUCLEIC acids , *POLYMER structure , *PROTEINS - Abstract
Emulsions have shown great potential in the delivery of various types of cargoes such as nucleic acids and proteins. In this study, fluorinated polymer emulsions (PFx@PFD-n) were prepared using fluorinated polymers with different structures as surfactant in PFD emulsions under ultrasound. These polymer emulsions gave comparable DNA binding ability compared with corresponding polymers. Heparin competition experiment showed that polymer emulsions could compact DNA or protein to form more stable complexes. In vitro gene transfection results showed that the polymer emulsions could induce higher gene expression than corresponding polymers and polyethyleneimine (PEI), and the transfection efficiency was enhanced with the increase of PFD amount in polymer emulsions. Flow cytometry studies revealed that the emulsions could mediate more efficient cellular uptake with stronger serum tolerance. Moreover, the polymer emulsion could deliver considerable amount of OVA into Raw 264.7 cells at low mass ratio, showing its potential in immunotherapy. The activities of β-galactosidase delivered by the emulsions could also be well maintained after entering cells. This study provides a strategy to construct cationic gene and cytosolic protein vectors with high efficiency and low toxicity. Image 1 • The improved delivery ability of fluorinated emulsion compared to polymer was investigated. • Emulsions with more PFD showed highest transfection efficiency. • Emulsions induced higher enzyme activity of β-Gal. • Emulsions exhibited higher serum stability and more efficient cell uptake. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
7. Rigid aromatic linking moiety in cationic lipids for enhanced gene transfection efficiency.
- Author
-
Wang, Bing, Zhao, Rui-Mo, Zhang, Ji, Liu, Yan-Hong, Huang, Zheng, Yu, Qing-Ying, and Yu, Xiao-Qi
- Subjects
- *
CATIONIC lipids , *STRUCTURE-activity relationships , *LINKAGE (Genetics) , *LIPIDS , *LIPOSOMES - Abstract
Although numerous cationic lipids have been developed as non-viral gene vectors, the structure-activity relationship (SAR) of these materials remains unclear and needs further investigation. In this work, a series of lysine-derived cationic lipids containing linkages with different rigidity were designed and synthesized. SAR studies showed that lipids with rigid aromatic linkage could promote the formation of tight liposomes and enhance DNA condensation, which is essential for the gene delivery process. These lipids could give much higher transfection efficiency than those containing more flexible aliphatic linkage in various cell lines. Moreover, the rigid aromatic linkage also affords the material higher serum tolerance ability. Flow cytometry assay revealed that the target lipids have good cellular uptake, while confocal microscopy observation showed weaker endosome escape than Lipofectamine 2000. To solve such problem and further increase the transfection efficiency, some lysosomotropic reagents were used to improve the endosome escape of lipoplex. As expected, higher transfection efficiency than Lipofectamine 2000 could be obtained via this strategy. Cytotoxicity assay showed that these lipids have lower toxicity in various cell lines than Lipofectamine 2000, suggesting their potential for further application. This work demonstrates that a rigid aromatic linkage might distinctly improve the gene transfection abilities of cationic lipids and affords information to construct safe and efficient gene vector towards practical application. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
8. Cyclen-based double-tailed lipids for DNA delivery: Synthesis and the effect of linking group structures.
- Author
-
Zhang, Yi-Mei, Chang, De-Chun, Zhang, Ji, Liu, Yan-Hong, and Yu, Xiao-Qi
- Subjects
- *
CYCLENS , *LIPID analysis , *DRUG delivery systems , *DNA synthesis , *GENE transfection , *CATIONIC lipids - Abstract
The gene transfection efficiency (TE) of cationic lipids is largely influenced by the lipid structure. Six novel 1, 4, 7, 10-tetraazacyclododecane (cyclen)-based cationic lipids L1 – L6 , which contain double oleyl as hydrophobic tails, were designed and synthesized. The difference between these lipids is their diverse backbone. Liposomes prepared by the lipids and DOPE showed good DNA affinity, and full DNA condensation could be achieved at N/P of 4 to form lipoplexes with proper size and zeta-potentials for gene transfection. Structure–activity relationship of these lipids as non-viral gene delivery vectors was investigated. It was found that minor backbone structural variations, including linking group and the structural symmetry would affect the TE. The diethylenetriamine derived lipid L4 containing amide linking bonds gave the best TE, which was several times higher than commercially available transfection reagent lipofectamine 2000. Besides, these lipids exhibited low cytotoxicity, suggesting their good biocompatibility. Results reveal that such type of cationic lipids might be promising non-viral gene vectors, and also afford us clues for the design of novel vectors with higher TE and biocompatibility. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
9. Low molecular weight PEI-based polycationic gene vectors via Michael addition polymerization with improved serum-tolerance.
- Author
-
Xun, Miao-Miao, Xiao, Ya-Ping, Zhang, Ji, Liu, Yan-Hong, Peng, Qi, Guo, Qian, Wu, Wan-Xia, Xu, Yong, and Yu, Xiao-Qi
- Subjects
- *
POLYMERIZATION , *POLYIONS , *MOLECULAR weights , *MICHAEL reaction , *GEL electrophoresis , *AGAROSE , *SERUM - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
10. ROS-responsive fluorinated polycations as non-viral gene vectors.
- Author
-
Zhang, Ju-Hui, Wang, Wei-Jia, Zhang, Ji, Xiao, Ya-Ping, Liu, Yan-Hong, and Yu, Xiao-Qi
- Subjects
- *
FLUOROBENZENE , *STRUCTURE-activity relationships , *SURFACE potential , *FLUOROPOLYMERS , *LIGHT scattering , *GEL electrophoresis , *GENES - Abstract
Polycation carriers hold great potential in gene therapy. However, they usually suffer from obvious cytotoxicity and unsatisfactory transfection efficiency. In this report, a series of fluorobenzene substituted and thioacetal contained polycations (TAEA-S-xF) were prepared to explore novel alternatives for safe and efficient non-viral polymeric gene vectors. The reactive oxygen species (ROS)-responsive property of thioacetal moieties together with the fluorine effect were hope to bring the vector better performance in gene delivery process. These materials could efficiently condense DNA into nanoparticles with proper size and surface potential. The structure-activity relationship of these materials was systematically investigated, and the In vitro transfection results revealed that the amount of fluorine atoms on the linkage plays important role to ensure the transfection efficiency and serum tolerance. The ROS-responsive behavior was verified by NMR, gel electrophoresis experiment and dynamic light scattering (DLS) assay. Cytotoxicity assay results also suggest that these ROS-degradable polycations show good biocompatibility in response to higher ROS level in cancer cells. Among these fluorinated polymers, the one with the most fluorine atoms showed the best transfection efficiency, which was up to 54 times higher than polyethyleneimine (PEI) 25 kDa. Mechanism studies reveal that its better performance may come from good cellular uptake and endosome escape ability. Image 1 • Novel ROS-responsive fluorobenzene-contained polymers were prepared for gene delivery. • ROS-responsive degradation could facilitate DNA release and diminish the cytotoxicity. • Fluorination degree influences the transfection efficiency and serum tolerance. • Polymer with most fluorine atoms showed much higher transfection efficiency than PEI. • The fluorination may also facilitate the cellular uptake and endosome escape ability. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.