A triple chain polycationic peptide-mimicking amphiphile – efficient DNA-transfer without co-lipids

2020 ◽  
Vol 8 (1) ◽  
pp. 232-249
Author(s):  
Shashank Reddy Pinnapireddy ◽  
Julia Giselbrecht ◽  
Boris Strehlow ◽  
Christopher Janich ◽  
Catharina Husteden ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Dna Transfer ◽  
Polycationic Peptide

DiTT4 lipoplexes have exhibited excellent transfection efficiency in a complex tissue together with a biocompatibility profile that makes it a prospective vehicle for gene delivery.

Stepwise Development of Biomimetic Chimeric Peptides for Gene Delivery

2020 ◽  
Vol 27 (8) ◽  
pp. 698-710
Author(s):  
Roya Cheraghi ◽  
Mahboobeh Nazari ◽  
Mohsen Alipour ◽  
Saman Hosseinkhani
Keyword(s):  
Gene Delivery ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
Large Scale ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Target Cells ◽  
Scale Production ◽  
Stepwise Development ◽  
Chimeric Peptides

Gene-based therapy largely relies on the vector type that allows a selective and efficient transfection into the target cells with maximum efficacy and minimal toxicity. Although, genes delivered utilizing modified viruses transfect efficiently and precisely, these vectors can cause severe immunological responses and are potentially carcinogenic. A promising method of overcoming this limitation is the use of non-viral vectors, including cationic lipids, polymers, dendrimers, and peptides, which offer potential routes for compacting DNA for targeted delivery. Although non-viral vectors exhibit reduced transfection efficiency compared to their viral counterpart, their superior biocompatibility, non-immunogenicity and potential for large-scale production make them increasingly attractive for modern therapy. There has been a great deal of interest in the development of biomimetic chimeric peptides. Biomimetic chimeric peptides contain different motifs for gene translocation into the nucleus of the desired cells. They have motifs for gene targeting into the desired cell, condense DNA into nanosize particles, translocate the gene into the nucleus and enhance the release of the particle into the cytoplasm. These carriers were developed in recent years. This review highlights the stepwise development of the biomimetic chimeric peptides currently being used in gene delivery.

scholarly journals Highly Osmotic Oxidized Sucrose-Crosslinked Polyethylenimine for Gene Delivery Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 87
Author(s):  
Jaehong Park ◽  
Kyusik Kim ◽  
Sohee Jeong ◽  
Migyeom Lee ◽  
Tae-il Kim
Keyword(s):  
Gene Delivery ◽  
Reductive Amination ◽  
Transfection Efficiency ◽  
Delivery Systems ◽  
Buffering Capacity ◽  
Serum Stability ◽  
High Osmolality ◽  
Cox 2 ◽  
Serum Free Conditions ◽  
Positively Charged

In this work, highly osmotic oxidized sucrose-crosslinked polyethylenimine (SP2K) polymers were developed for gene delivery systems, and the transfection mechanism is examined. First, periodate-oxidized sucrose and polyethylenimine 2K (PEI2K) were crosslinked with various feed ratios via reductive amination. The synthesis was confirmed by 1H NMR and FTIR. The synthesized SP2K polymers could form positively charged (~40 mV zeta-potential) and nano-sized (150–200 nm) spherical polyplexes with plasmid DNA (pDNA). They showed lower cytotoxicity than PEI25K but concentration-dependent cytotoxicity. Among them, SP2K7 and SP2K10 showed higher transfection efficiency than PEI25K in both serum and serum-free conditions, revealing the good serum stability. It was found that SP2K polymers possessed high osmolality and endosome buffering capacity. The transfection experiments with cellular uptake inhibitors suggest that the transfection of SP2K polymers would progress by multiple pathways, including caveolae-mediated endocytosis. It was also thought that caveolae-mediated endocytosis of SP2K polyplexes would be facilitated through cyclooxygenase-2 (COX-2) expression induced by high osmotic pressure of SP2K polymers. Confocal microscopy results also supported that SP2K polyplexes would be internalized into cells via multiple pathways and escape endosomes efficiently via high osmolality and endosome buffering capacity. These results demonstrate the potential of SP2K polymers for gene delivery systems.

Boosting transfection efficiency: A systematic study using layer-by-layer based gene delivery platform

2021 ◽  
pp. 112161
Author(s):  
Yana V. Tarakanchikova ◽  
Dmitrii S. Linnik ◽  
Tatiana Mashel ◽  
Albert R. Muslimov ◽  
Sergey Pavlov ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Systematic Study ◽  
Transfection Efficiency ◽  
Layer By Layer ◽  
Delivery Platform

scholarly journals Electrical Field-Assisted Gene Delivery from Polyelectrolyte Multilayers

Polymers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 133
Author(s):  
Yu-Che Cheng ◽  
Shu-Lin Guo ◽  
Kun-Da Chung ◽  
Wei-Wen Hu
Keyword(s):  
Gene Delivery ◽  
Electric Field ◽  
Treatment Time ◽  
Transfection Efficiency ◽  
Polyelectrolyte Multilayers ◽  
Aqueous Environment ◽  
Layer By Layer ◽  
Electrical Field ◽  
Lbl Assembly ◽  
Electric Field Treatment

To sustain gene delivery and elongate transgene expression, plasmid DNA and cationic nonviral vectors can be deposited through layer-by-layer (LbL) assembly to form polyelectrolyte multilayers (PEMs). Although these macromolecules can be released for transfection purposes, their entanglement only allows partial delivery. Therefore, how to efficiently deliver immobilized genes from PEMs remains a challenge. In this study, we attempt to facilitate their delivery through the pretreatment of the external electrical field. Multilayers of polyethylenimine (PEI) and DNA were deposited onto conductive polypyrrole (PPy), which were placed in an aqueous environment to examine their release after electric field pretreatment. Only the electric field perpendicular to the substrate with constant voltage efficiently promoted the release of PEI and DNA from PEMs, and the higher potential resulted in the more releases which were enhanced with treatment time. The roughness of PEMs also increased after electric field treatment because the electrical field not only caused electrophoresis of polyelectrolytes and but also allowed electrochemical reaction on the PPy electrode. Finally, the released DNA and PEI were used for transfection. Polyplexes were successfully formed after electric field treatment, and the transfection efficiency was also improved, suggesting that this electric field pretreatment effectively assists gene delivery from PEMs and should be beneficial to regenerative medicine application.

scholarly journals Selective Modification of Chitosan to Enable the Formation of Chitosan-DNA Condensates by Electron Donator Stabilization

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Karl E. Kador ◽  
Anuradha Subramanian
Keyword(s):  
Drug Delivery ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
Protonated Form ◽  
Chemical Modifications ◽  
Modified Chitosan

Chitosan, a polyaminosaccharide, has been investigated for its use in the field of drug-delivery and biomaterial applications because of its natural biocompatibility and polycationic properties. Chemical modifications of chitosan have been attempted in an effort to increase the transfection efficiency with respect to gene delivery applications; however, it is unknown how these modifications affect the formation of the condensates. This study attempts to determine the effects of modification of the cationic center of chitosan on the ability to condense DNA. Specifically, electron-donating or -withdrawing groups were used as modifiers of the cationic charge on the chitosan backbone to stabilize the protonated form of chitosan, which is necessary to form condensates and increase the efficiency of the polymer to condense DNA by yielding condensates at a lower nitrogen to phosphorous (N : P) ratio. While an N : P ratio of 7 is needed to condense DNA with unmodified chitosan, phthalate-modified chitosan yielded condensates were obtained at an N : P ratio of 1.0.

scholarly journals Synthesis, and Characterization, and Evaluation of Cellular Effects of the FOL-PEG-g-PEI-GAL Nanoparticles as a Potential Non-Viral Vector for Gene Delivery

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
S. Ghiamkazemi ◽  
A. Amanzadeh ◽  
R. Dinarvand ◽  
M. Rafiee-Tehrani ◽  
M. Amini
Keyword(s):  
Gene Delivery ◽  
Zeta Potential ◽  
Surface Charge ◽  
Cell Line ◽  
Graft Copolymer ◽  
Viral Vector ◽  
Transfection Efficiency ◽  
High Surface ◽  
Liver Cells ◽  
Dna Complexes

In this manuscript, we synthesized the potential non viral vector for gene delivery with proper transfection efficiency and low cytotoxicity. Polyethylenimine (PEI) is a well-known cationic polymer which has high positive surface charge for condensing plasmid DNA. However; it is highly cytotoxic in many cell lines because of the high surface charge, non-biodegradability and non-biocompatibility. To enhance PEI biodegradability, the graft copolymer “PEG-g-PEI” was synthesized. To target cancer liver cells, two targeting ligands folic acid and galactose (lactobionic acid) which are over expressed on human hepatocyte carcinoma were attached to graft copolymer and “FOL-PEG-g-PEI-GAL” copolymer was synthesized. Composition of this grafted copolymer was characterized using1H-NMR and FTIR spectra. The molecular weight and zeta potential of this copolymer was compared to PEI. The particle size and zeta potential of FOL-PEG-g-PEI-GAL/DNA complexes at various N/P ratio were measured using dynamic light scattering (DLS). Cytotoxicity of the copolymer was also studied in cultured HepG2 human hepatoblastoma cell line. The FOL-PEG-g-PEI-GAL/DNA complexes at various N/P ratios exhibited no cytotoxicity in HepG2 cell line compared to PEI 25K as a control. The novel copolymer showed enhanced biodegradability in physiological conditions in compared with PEI and targeted cultured HepG2 cells. More importantly, significant transfection efficiency was exhibited in cancer liver cells. Together, our results showed that “FOL-PEG-g-PEI-GAL” nanoparticals could be considered as a useful non-viral vector for targeted gene delivery.

Cationic amphiphilic calixarenes to compact DNA into small nanoparticles for gene delivery

2015 ◽  
Vol 39 (3) ◽  
pp. 1654-1664 ◽  
Author(s):  
Roman V. Rodik ◽  
Anne-Sophie Anthony ◽  
Vitaly I. Kalchenko ◽  
Yves Mély ◽  
Andrey S. Klymchenko
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Alkyl Chains ◽  
Dna Nanoparticles ◽  
Small Nanoparticles

Cationic amphiphilic calixarenes with longer alkyl chains are less cytotoxic and their virus-sized DNA nanoparticles exhibit higher transfection efficiency.

Flexible cyclic siloxane core enhances the transfection efficiency of polyethylenimine-based non-viral gene vectors

2015 ◽  
Vol 3 (42) ◽  
pp. 8250-8267 ◽  
Author(s):  
Cristina M. Uritu ◽  
Manuela Calin ◽  
Stelian S. Maier ◽  
Corneliu Cojocaru ◽  
Alina Nicolescu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Viral Gene ◽  
Cyclic Siloxane ◽  
Gene Vectors

cD4H–AGE–PEI conjugates, with a favorable balance between hydrophilic and hydrophobic moieties, are promising carriers for gene delivery.

scholarly journals Synthesis, characterization and evaluation of transfection efficiency of dexamethasone conjugated poly(propyleneimine) nanocarriers for gene delivery#

2018 ◽  
Vol 56 (1) ◽  
pp. 519-527 ◽  
Author(s):  
Bizhan Malaekeh-Nikouei ◽  
Mehdi Rezaee ◽  
Leila Gholami ◽  
Naghmeh Sanjar Mousavi ◽  
Reza Kazemi Oskuee
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency

Evaluation of low molecular weight polyethylenimine-introduced chitosan for gene delivery to mesenchymal stem cells

2020 ◽  
Vol 10 (7) ◽  
pp. 1170-1176
Author(s):  
Minchen Liu ◽  
Yulan Hu ◽  
Yi Feng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
A549 Cells ◽  
Safety Evaluation ◽  
Physicochemical Characteristics ◽  
Hatching Rate

This study aimed to examine the transfection ability of polyethylenimine (PEI) (1800 Da)-grafted chitosan (10 kDa) (CP), a newly synthesized PEI derivative, in mesenchymal stem cells (MSCs). The safety evaluation of the complex/DNA was studied in vitro and in vivo. In addition, CP/pGL3 was applied to investigate the effects of transfection efficiency. In this study, CP/DNA can be formed with compatible physicochemical characteristics for gene delivery. CP cytotoxicity decreased in A549 cells. Moreover, a zebrafish embryo model was used for evaluating the safety in vivo. Compared to the PEI (25 kDa) group, the zebrafish hatching rate increased and the mortality rate decreased in the CP/DNA group, which provided an indication of the safety of CP. In comparison with chitosan (100 kDa)-PEI (1200 Da), CP's transfection efficiency was higher in both A549 cells and MSCs. This study aimed to lay the foundation for further applications of CP in gene delivery. Therefore, further gene therapy investigations of CP by using MSCs need to be performed.

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