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

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.

2016 ◽  
Vol 4 (12) ◽  
pp. 2208-2218 ◽  
Author(s):  
Young-Dong Kim ◽  
Tae-Eun Park ◽  
Bijay Singh ◽  
Kye-Soo Cho ◽  
Jaiprakash N. Sangshetti ◽  
...  

A new polylactitol-based multifunctional gene carrier has shown low cytotoxicity, a high transfection efficiency, and liver cell targeting bothin vitroandin vivo.


2007 ◽  
Vol 342-343 ◽  
pp. 521-524
Author(s):  
Oju Jeon ◽  
Su Jin Song ◽  
Min Hyung Lee ◽  
Sang Woo Seo ◽  
Cha Yong Choi ◽  
...  

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.


2021 ◽  
Author(s):  
Zikun Yu ◽  
Zhimin Zhang ◽  
Jing Yan ◽  
Ziyin Zhao ◽  
Chenglong Ge ◽  
...  

Guanidine-rich helical polypeptides bearing hydrophobic amino acid pendants displayed high transfection efficiency both in vitro and in vivo and low cytotoxicity toward applications in gene therapy.


2017 ◽  
Vol 5 (11) ◽  
pp. 2328-2336 ◽  
Author(s):  
Mathias Dimde ◽  
Falko Neumann ◽  
Felix Reisbeck ◽  
Svenja Ehrmann ◽  
Jose Luis Cuellar-Camacho ◽  
...  

An advanced cationic carrier system which combines high transfection efficiency with low cytotoxicity and a control over the release of the encapsulated genetic material by the reduction of the multivalent architecture upon pH triggered degradation was developed.


RSC Advances ◽  
2012 ◽  
Vol 2 (10) ◽  
pp. 4335 ◽  
Author(s):  
Soma Patnaik ◽  
Ritu Goyal ◽  
Sushil K. Tripathi ◽  
Mohammed Arif ◽  
Kailash C. Gupta

2016 ◽  
Vol 4 (39) ◽  
pp. 6462-6467 ◽  
Author(s):  
Sheng-Gang Ding ◽  
Lei Yu ◽  
Long-Hai Wang ◽  
Lin-Ding Wang ◽  
Zhi-Qiang Yu ◽  
...  

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


2015 ◽  
Vol 3 (6) ◽  
pp. 1068-1078 ◽  
Author(s):  
Liang Luan ◽  
Qingbin Meng ◽  
Liang Xu ◽  
Zhao Meng ◽  
Husheng Yan ◽  
...  

A series of peptides containing multiple functional fragments were designed as gene-delivery vectors with transfection efficiency comparable to Lipofectamine 2000.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yinan Zhao ◽  
Tianyi Zhao ◽  
Yanyan Du ◽  
Yingnan Cao ◽  
Yang Xuan ◽  
...  

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.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ana V. Oliveira ◽  
Diogo B. Bitoque ◽  
Gabriela A. Silva

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.


2015 ◽  
Vol 68 (5) ◽  
pp. 806 ◽  
Author(s):  
Liandong Feng ◽  
Xinyu Hu ◽  
Aming Xie ◽  
Hao Yu ◽  
Yangyang Liu ◽  
...  

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.


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