Synthesis and Characterization of Polyethylenimine-Graft-Poly(L-Lactide-Co-Glycolide) Block Copolymers for Gene Delivery

2007 ◽  
Vol 342-343 ◽  
pp. 521-524
Author(s):  
Oju Jeon ◽  
Su Jin Song ◽  
Min Hyung Lee ◽  
Sang Woo Seo ◽  
Cha Yong Choi ◽  
...  
Keyword(s):  
Block Copolymers ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Gel Permeation Chromatography ◽  
Copolymer Composition ◽  
High Gene ◽  
Good Biocompatibility ◽  
Delivery Vehicles

Polyethylenimine-graft-poly(L-lactide-co-glycolide) (PEI-g-PLGA) block copolymers were prepared by a ring-opening polymerization of L-lactide and glycolide using PEI as a macroinitiator and stannous octoate as a catalyst in dimethylformamide at 100 °C. The molecular structure of the block copolymers was evaluated with 1H-NMR, and the molecular weight of the block copolymers was determined with gel permeation chromatography. The thermal properties were investigated using differential scanning calorimetery and thermogravimetric analysis. The zetapotential of the pDNA/copolymer complexes was evaluated with dynamic laser light scattering. Cytotoxicity and gene transfection efficiency of PEI-g-PLGA were tested in vitro using human embryonic kidney 293 cell culture. The pDNA/copolymer complexes (N/P = 10) showed a lower zeta-potential than pDNA/PEI25kDa complex, suggesting the lower toxicity of the pDNA/copolymer complexes. The copolymer composition was found to significantly affect the gene transfection efficiency of the pDNA/copolymer complexes. The copolymers with lower contents of PLGA showed higher gene transfection efficiency. These results indicate that these block copolymers are promising candidates for gene delivery vehicles, featuring good biocompatibility, potential biodegradability, and relatively high gene transfection efficiency.

scholarly journals Aromatic Thioacetal-Bridged ROS-Responsive Nanoparticles as Novel Gene Delivery Vehicles

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2061 ◽  
Author(s):  
Guo-Qing Lin ◽  
Wen-Jing Yi ◽  
Qiang Liu ◽  
Xue-Jun Yang ◽  
Zhi-Gang Zhao
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Zeta Potentials ◽  
Sar Studies ◽  
Gene Delivery Vectors ◽  
Efficient Gene ◽  
Delivery Vehicles ◽  
Low Cytotoxicity

In this report, a series of polycations are designed and synthesized by conjugating reactive oxygen species (ROS)-responsive thioacetal-linkers to low molecular weight (LMW) polyethylenimine (PEI) via ring-opening polymerization. Their structure–activity relationships (SARs) as gene delivery vectors are systematically studied. Although the MWs of the target polymers are only ~9 KDa, they show good DNA binding ability. The formed polyplexes, which are stable toward serum but decomposed under ROS-conditions, have appropriate sizes (180~300 nm) and positive zeta-potentials (+35~50 mV). In vitro experiments reveal that these materials have low cytotoxicity, and higher transfection efficiency (TE) than controls. Furthermore, the title polymers exhibit excellent serum tolerance. With the present of 10% serum, the TE of the polymers even increases up to 10 times higher than 25 KDa PEI and 9 times higher than Lipofectamine 2000. The SAR studies also reveal that electron-withdrawing groups on the aromatic ring in 4a may benefit to balance between the DNA condensation and release for efficient gene transfection.

scholarly journals Aminated β-Cyclodextrin-Modified-Carboxylated Magnetic Cobalt/Nanocellulose Composite for Tumor-Targeted Gene Delivery

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Thayyath Sreenivasan Anirudhan ◽  
Sylaja Raveendran Rejeena
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Luciferase Expression ◽  
High Dose ◽  
Targeted Gene Delivery ◽  
Life Threatening ◽  
High Gene ◽  
Good Biocompatibility ◽  
Potential Biodegradability

Gene therapy is a new kind of medicine, which uses genes as drugs in order to treat life threatening diseases. In the present work, a nonviral vector, aminated β-cyclodextrin-modified-carboxylated magnetic cobalt/nanocellulose composite (ACDC-Co/NCC), was synthesized for efficient transfection of genes into tumour cells. The synthesized ACDC-Co/NCC was characterized by means of FTIR, XRD, SEM, and ESR techniques. DNA condensing ability of ACDC-Co/NCC was found to be increased with increase in amount of ACDC-Co/NCC and 84.9% of DNA (1.0 μg/mL) inclusion was observed with 6.0 μg/mL of ACDC-Co/NCC. The cytotoxicity of ACDC-Co/NCC was observed to be minimal, even at higher concentration, with respect to the model transfecting agent, poly(ethyleneimine) (PEI). 88.2% of the gene was transfected at high dose of DNA, as indicated by the highest luciferase expression. These results indicated that ACDC-Co/NCC might be a promising candidate for gene delivery with the characteristics of good biocompatibility, potential biodegradability, minimal cytotoxicity, and relatively high gene transfection efficiency.

Self-assembling Janus dendritic polymer for gene delivery with low cytotoxicity and high gene transfection efficiency

2016 ◽  
Vol 4 (39) ◽  
pp. 6462-6467 ◽  
Author(s):  
Sheng-Gang Ding ◽  
Lei Yu ◽  
Long-Hai Wang ◽  
Lin-Ding Wang ◽  
Zhi-Qiang Yu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Dendritic Polymer ◽  
Self Assembling ◽  
High Gene ◽  
Low Cytotoxicity

Polycations have high DNA condensing ability, low immunogenicity, and great adaptability, which make them promising for gene delivery.

scholarly journals Interaction kinetics of peptide lipids-mediated gene delivery

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yinan Zhao ◽  
Tianyi Zhao ◽  
Yanyan Du ◽  
Yingnan Cao ◽  
Yang Xuan ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Endosomal Escape ◽  
Late Endosomes ◽  
Key Factor ◽  
Interaction Kinetics ◽  
Dna Release

Abstract Background During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency. Results As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp (− 0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the “proton sponge effect” of the lipid. Conclusions The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

scholarly journals Combining Hyaluronic Acid with Chitosan Enhances Gene Delivery

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ana V. Oliveira ◽  
Diogo B. Bitoque ◽  
Gabriela A. Silva
Keyword(s):  
Hyaluronic Acid ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Nonviral Vectors ◽  
Anionic Polymer ◽  
Dna Release

The low gene transfer efficiency of chitosan-DNA polyplexes is a consequence of their high stability and consequent slow DNA release. The incorporation of an anionic polymer is believed to loosen chitosan interactions with DNA and thus promote higher transfection efficiencies. In this work, several formulations of chitosan-DNA polyplexes incorporating hyaluronic acid were prepared and characterized for their gene transfection efficiency on both HEK293 and retinal pigment epithelial cells. The different polyplex formulations showed morphology, size, and charge compatible with a role in gene delivery. The incorporation of hyaluronic acid rendered the formulations less stable, as was the goal, but it did not affect the loading and protection of the DNA. Compared with chitosan alone, the transfection efficiency had a 4-fold improvement, which was attributed to the presence of hyaluronic acid. Overall, our hybrid chitosan-hyaluronic acid polyplexes showed a significant improvement of the efficiency of chitosan-based nonviral vectorsin vitro, suggesting that this strategy can further improve the transfection efficiency of nonviral vectors.

Cationic Charged Polymer Vesicles from Amphiphilic PEI-g-PSSA-g-PEI as Potential Gene Delivery Vehicles

2015 ◽  
Vol 68 (5) ◽  
pp. 806 ◽  
Author(s):  
Liandong Feng ◽  
Xinyu Hu ◽  
Aming Xie ◽  
Hao Yu ◽  
Yangyang Liu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Self Assembly ◽  
Transfection Efficiency ◽  
Hexagonal Structure ◽  
Polymer Vesicles ◽  
Small Series ◽  
Transmission Electron ◽  
Delivery Vehicles ◽  
Insoluble Polymers

Polymer vesicles have attracted extensive interest for a variety of biomedical applications. Herein, novel polymer vesicles are prepared by the self-assembly of amphiphilic polyethyleneimine-g-poly(disulfide amine)-g-polyethyleneimine (PEI-g-PSSA-g-PEI) for gene delivery. To investigate the effect of hydrophobicity on transfection efficiency, a small series of PEI-g-PSSA-g-PEI were prepared under uniform conditions containing PEI fragments of the same molecular weight. The hydrophobicity of PEI-g-PSSA-g-PEI was adjusted by varying the hydrophobic content in the poly(disulfide amine) backbone and by choosing hydrophobic monomers ranging in length from C12 to C16. The hydrophobicity of polymers was also related to DNA binding affinity. Polymer vesicles obtained from the water-insoluble polymers condensed with DNA into polyplexes with sizes below 200 nm and surface charge ranging from +10 to +35 mV that were suitable for cell endocytosis. DNA polyplexes exhibited an inverted hexagonal structure, observed by transmission electron microscopy. The results of in vitro transfection demonstrate that the hydrophobic–hydrophilic balance of copolymers greatly affects their transfection properties. The top-performing polymer, II-70 %, showed improved transfection efficiency and significantly lower cytotoxicity on COS-7 cells when compared with commercial reagents polyethyleneimine (PEI 25K) and Lipofectamine 2000. These results indicate that cationic polymer vesicles with tunable hydrophobicity are promising materials for gene delivery.

Functional Amphiphiles for Gene Delivery

MRS Bulletin ◽  
2005 ◽  
Vol 30 (9) ◽  
pp. 647-653 ◽  
Author(s):  
Philippe Barthélémy ◽  
Michel Camplo
Keyword(s):  
Gene Transfer ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Research Activity ◽  
Safety Issues ◽  
Significant Research

AbstractThe design of safe and efficient gene transfer vectors remains one of the key challenges in gene therapy. Despite their remarkable transfection efficiency, viral vectors suffer from known safety issues. Consequently, significant research activity has been undertaken to develop nonviral approaches to gene transfer during the last decade. Numerous academic and industrial research groups are investigating synthetic cationic vectors, such as cationic amphiphiles, with the objective of increasing the gene transfection activity. Within this area, the development of functional synthetic vectors that respond to local environmental effects have met with success. These synthetic vectors are based on mechanistic principles and represent a significant departure from earlier systems. Many of these systems for gene delivery in vitro and in vivo are discussed in this article.

scholarly journals Interaction Kinetics of Peptide Lipids-Mediated Gene Delivery

2019 ◽  
Author(s):  
Shubiao Zhang ◽  
Yinan Zhao ◽  
Yanyan Du ◽  
Yingnan Cao ◽  
Yang Xuan ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Endosomal Escape ◽  
Late Endosomes ◽  
Key Factor ◽  
Interaction Kinetics ◽  
Dna Release

Abstract Background: During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency.Results: As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp(-0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in Hela cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplexes was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the “proton sponge effect” of the lipid.Conclusions: The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

The Combination of Drug or Gene Delivery System Responding to Cellular Signals (D-RECS) and Sonoporation System for Effective and Safe Gene Delivery

2009 ◽  
Vol 1237 ◽  
Author(s):  
Akira Tsuchiya ◽  
Takeshi Mori ◽  
Yuki Naritomi ◽  
Jeong-Hun Kang ◽  
Daisuke Asai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Gene Delivery ◽  
Delivery System ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Regulation System ◽  
Gene Delivery System

AbstractWe have developed new gene expression-regulating polymer that can activate transgene expression in response to target intracellular signals. Here, we tried applying sonoporation system to this gene regulation system to enhance the gene expression efficacy. Sonoporation is the method for effective gene transfection in vitro and in vivo. Therefore, the method might enhance the transfection efficiency in our polymer and realize an efficient and safe gene delivery system. Results suggested that the combination of our polymer and sonoporation could improve the gene expression compared to the system using only our polymer that transfers genes into cells via endocytosis. It also kept the ability of the gene regulation responding to cellular signals.

Continuous Vector-free Gene Transfer with a Novel Microfluidic Chip and Nanoneedle Array

2018 ◽  
Vol 16 (2) ◽  
pp. 164-170 ◽  
Author(s):  
Dong Huang ◽  
Deyao Zhao ◽  
Jinhui Li ◽  
Yuting Wu ◽  
Lili Du ◽  
...  
Keyword(s):  
Microfluidic Chip ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Basic Research ◽  
Nanoneedle Array ◽  
Contact Frequency ◽  
Delivery Platform ◽  
High Gene ◽  
Free Gene

Background: Delivery of foreign cargoes into cells is of great value for bioengineering research and therapeutic applications. Objective: In this study, we proposed and established a carrier-free gene delivery platform utilizing staggered herringbone channel and silicon nanoneedle array, to achieve high-throughput in vitro gene transfection. </P><P> Methods: With this microchip, fluidic micro vortices could be induced by the staggered-herringboneshaped grooves within the channel, which increased the contact frequency of the cells with the channel substrate. Transient disruptions on the cell membrane were well established by the nanoneedle array on the substrate. </P><P> Result: Compared to the conventional nanoneedle-based delivery system, proposed microfluidic chip achieved flow-through treatment with high gene transfection efficiency (higher than 20%) and ideal cell viability (higher than 95%). It provides a continuous processing environment that can satisfy the transfection requirement of large amounts of biological molecules, showing high potential and promising prospect for both basic research and clinical application.

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