A PEG-b-poly(disulfide-l-lysine) based redox-responsive cationic polymer for efficient gene transfection

2019 ◽  
Vol 7 (11) ◽  
pp. 1893-1905 ◽  
Author(s):  
Ihsan Ullah ◽  
Jing Zhao ◽  
Shah Rukh ◽  
Khan Muhammad ◽  
Jintang Guo ◽  
...  

A redox responsive gene vector efficiently delivered pDNA with a good internalization tendency, efficient endosomal escape and high nucleus internalization.

2020 ◽  
Author(s):  
Shikun Zhang ◽  
Lin Gong ◽  
Xue Zhang ◽  
Zhi-min Yun ◽  
Su-Bo Li ◽  
...  

Abstract Background:pH-sensitive peptides are a relatively new strategy for conquering poor endosomal release of cationic polymer-mediated transfection. Modification of antimicrobial peptides (AMPs) by exchanging positively-charged residues with negatively-charged glutamic acid residues (Glu) greatly improved its lytic activity at the endosomal pH, which could improve cationic polymer-mediated transfection.Methods:In the present study, we investigate the effect of the number of Glu substituted for positively-charged residues on the endosomal escape activity of AR-23 and the ability of mutated AR-23 for enhancing cationic polymer-mediated transfection. Three analogs were synthesized by replacing the positively-charged residues in AR-23's sequence with Glu one-by-one. The pH-sensitive lysis ability of the peptides, the effect of peptides on the physicochemical characteristics, the intracellular trafficking,the transfection efficiency, and the cytotoxicity of the polyplexes were determined.Results:Increased lytic activity of peptides was observed with the increased number of Glu replacement in the AR-23 sequence at acidic pH. The number of Glu substituted for positively-charged residues of AR-23 dramatically affects its lysis ability at neutral pH. Triple-Glu substitution in AR-23's sequence greatly improved PLL-mediated gene transfection efficiency while maintaining low cytotoxicity.Conclusion:The results indicate that replacement of positively-charged residues with enough Glu residues may be considered a method for designing pH-sensitive peptides, which could be applied as potential enhancers for improving cationic polymer-mediated transfection.


Soft Matter ◽  
2010 ◽  
Vol 6 (5) ◽  
pp. 955 ◽  
Author(s):  
Dan Chen ◽  
Yuan Ping ◽  
Guping Tang ◽  
Jun Li

2020 ◽  
Vol 8 (33) ◽  
pp. 7475-7482
Author(s):  
De-E Liu ◽  
Xiangjie Yan ◽  
Jinxia An ◽  
Jianbiao Ma ◽  
Hui Gao

A novel virus-mimicking gene delivery system with excellent endosomal escape, efficient transfection, and traceability is developed which can serve as a reference for the construction of novel multifunctional efficient gene delivery systems.


2015 ◽  
Vol 13 (14) ◽  
pp. 4310-4320 ◽  
Author(s):  
Gururaja Vulugundam ◽  
Krishan Kumar ◽  
Paturu Kondaiah ◽  
Santanu Bhattacharya

New redox-active monomeric and dimeric ferrocenylated cationic cholesterols for gene transfection.


2010 ◽  
Vol 21 (6) ◽  
pp. 1087-1095 ◽  
Author(s):  
Kai-Ling Chang ◽  
Yuriko Higuchi ◽  
Shigeru Kawakami ◽  
Fumiyoshi Yamashita ◽  
Mitsuru Hashida

Molecules ◽  
2016 ◽  
Vol 21 (8) ◽  
pp. 1103 ◽  
Author(s):  
Qi Lei ◽  
Jing-Jing Hu ◽  
Lei Rong ◽  
Han Cheng ◽  
Yun-Xia Sun ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1964
Author(s):  
Huaiying Zhang ◽  
Damla Keskin ◽  
Willy H. de Haan-Visser ◽  
Guangyue Zu ◽  
Patrick van Rijn ◽  
...  

Gene therapy is a promising treatment for hereditary diseases, as well as acquired genetic diseases, including cancer. Facing the complicated physiological and pathological environment in vivo, developing efficient non-viral gene vectors is needed for their clinical application. Here, poly(N-isopropylacrylamide) (p(NIPAM)) nanogels are presented with either protonatable tertiary amine groups or permanently charged quaternized ammonium groups to achieve DNA complexation ability. In addition, a quaternary ammonium-functionalized nanogel was further provided with an aliphatic moiety using 1-bromododecane to add a membrane-interacting structure to ultimately facilitate intracellular release of the genetic material. The ability of the tertiary amine-, quaternized ammonium-, and aliphatic quaternized ammonium-functionalized p(NIPAM) nanogels (i.e., NGs, NGs-MI, and NGs-BDD, respectively) to mediate gene transfection was evaluated by fluorescence microscopy and flow cytometry. It is observed that NGs-BDD/pDNA complexes exhibit efficient gene loading, gene protection ability, and intracellular uptake similar to that of NGs-MI/pDNA complexes. However, only the NGs-BDD/pDNA complexes show a notable gene transfer efficiency, which can be ascribed to their ability to mediate DNA escape from endosomes. We conclude that NGs-BDD displays a cationic lipid-like behavior that facilitates endosomal escape by perturbing the endosomal/lysosomal membrane. These findings demonstrate that the presence of aliphatic chains within the nanogel is instrumental in accomplishing gene delivery, which provides a rationale for the further development of nanogel-based gene delivery systems.


2018 ◽  
Vol 32 (4) ◽  
pp. 982-987 ◽  
Author(s):  
Hui Zhang ◽  
Jiawei Tu ◽  
Yangying Liao ◽  
Kuan Cai ◽  
Yue Li ◽  
...  

2017 ◽  
Vol 53 (59) ◽  
pp. 8328-8331 ◽  
Author(s):  
Jamie C. Gaitor ◽  
Lauren M. Paul ◽  
Melissa M. Reardon ◽  
Taha Hmissa ◽  
Samuel Minkowicz ◽  
...  

Novel lipidic ionic liquids with imidazolium headgroups (red), thioether linkers (black), and two hydrophobic tails (blue) as efficient gene transfection vectors, synthesized via thiol–yne click chemistry.


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