2-Amino-6-chloropurine-modified polyamidoamine-mediated p53 gene transfection to achieve anti-tumor efficacy

2018 ◽  
Vol 42 (16) ◽  
pp. 13375-13381 ◽  
Author(s):  
Haobo Han ◽  
Wenqi Chen ◽  
Jiebing Yang ◽  
Jiayuan Zhang ◽  
Quanshun Li ◽  
...  

The modification of 2-amino-6-chloropurine on polyamidoamine was performed to synthesize a derivative, AP-PAMAM, which was then employed as a carrier for p53 gene delivery to achieve anti-tumor efficacy.

2020 ◽  
Vol 8 (41) ◽  
pp. 9555-9565 ◽  
Author(s):  
Lei Li ◽  
Hongrui Tian ◽  
Jinlin He ◽  
Mingzu Zhang ◽  
Zuguang Li ◽  
...  

Aminated poly(glycidyl methacrylate)-based polymers for gene delivery not only can reduce toxicity and improve solubility, but can improve gene transfection efficiency and reduce protein aggregation.


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.


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.


2001 ◽  
Author(s):  
Koji Endo ◽  
Itaru Kuratate ◽  
Mari Watanabe ◽  
Haruhiko Yoshida ◽  
Ryota Teshima ◽  
...  

RSC Advances ◽  
2014 ◽  
Vol 4 (73) ◽  
pp. 38623-38629 ◽  
Author(s):  
Chao-Qun Wang ◽  
Meng-Qing Gong ◽  
Jin-Long Wu ◽  
Ren-Xi Zhuo ◽  
Si-Xue Cheng

Dual-functionalized KALA/PS/CaCO3/DNA nanoparticles containing a cell penetrating peptide (KALA) and protamine sulfate (PS) could effectively mediate gene transfection at a low DNA concentration.


1995 ◽  
Vol 17 (3) ◽  
pp. 209-216 ◽  
Author(s):  
Behnam Badie ◽  
Kenneth E. Drazan ◽  
Mark H. Krama ◽  
Abraham Shaked ◽  
Keith L. Black

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22018-e22018
Author(s):  
Zhengchao Tao ◽  
Liting Qian

e22018 Background: Several studies demonstrated that p53 gene transfection enhanced the anti-tumor effects of radiotherapy. This study is to investigate whether p53 gene transfection can increase the radiosensitivity of liver tumor cells. Methods: Liver tumor cell lines, HepG2 (with wild type p53 genes) and PLC/PRF/5 (with mutant p53 genes), were separately transfected with recombinant adenoviral human p53 gene (rAdp53) and adenoviral enhance green fluorescent protein gene (AdEGFP), forming 4 types of cells: HepG2 transfected with rAdp53, HepG2 with AdEGFP, PLC/PRF/5 with rAdp53, and PLC/PRF/5 with AdEGFP. The transfected and untransfected HepG2 and PLC/PRF/5 cells were irradiated with 6MV-X at doses of 0, A2, A4, A6, A8, A and 10 Gy. After exposition to radiation, cell survival, clonogenic capacity, and apoptosis were analyzed. The effect differences between cell types were analyzed using statistical methods of pairwise group comparisons and mixed effect model. Results: After exposing irradiation, all the cells’ survival rate and clonogenic capacity decreased, and the proportion of apoptotic cell increased. These effects become stronger with increaseing dose of radiation. Between untransfected cells, radiation had a stronger effect on HepG2 cells than PLC/PRF/5 and the differences were statistically significant for all the 3 measures. The rAdp53 transfection, not the AdEGFP, significantly enhanced radiation effects on both cell lines. The enhanced effects on PLC/PRF/5 cells were significantly stronger then the enhanced effects on HepG2 cells. Conclusions: PLC/PRF/5 cells with mutant p53 genes were more resistant to radiation then HepG2 with wide type of p53 genes. The rAd-P53 transfection could enhance radiosensitivity of both cell lines, but the enhanced effect on PLC/PRF/5 cells with mutant p53 gene was stronger than HepG2 with wide type of p53 genes.


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