New multivalent cationic lipids reveal bell curve for transfection efficiency versus membrane charge density: lipid-DNA complexes for gene delivery

2005 ◽  
Vol 7 (6) ◽  
pp. 739-748 ◽  
Author(s):  
Ayesha Ahmad ◽  
Heather M. Evans ◽  
Kai Ewert ◽  
Cyril X. George ◽  
Charles E. Samuel ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Charge Density ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Dna Complexes ◽  
Bell Curve ◽  
Membrane Charge

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 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.

Cholic Acid-Modified Polyethylenimine for Gene Delivery into Human Carcinoma Cells

2014 ◽  
Vol 1060 ◽  
pp. 3-6 ◽  
Author(s):  
Wanlop Weecharangsan ◽  
Orapan Paecharoenchai ◽  
Nattisa Niyomtham ◽  
Praneet Opanasopit ◽  
Boon-ek Yingyongnarongkul ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Zeta Potential ◽  
Cholic Acid ◽  
Plasmid Dna ◽  
Gel Electrophoresis ◽  
Transfection Efficiency ◽  
Carcinoma Cells ◽  
Molar Ratio ◽  
Dna Complexes ◽  
Human Carcinoma

Polyethylenimine (PEI) was modified by cholic acid at a molar ratio of 1:1. Cholic acid (CA)-modified PEI (PEI-CA) were evaluated for formation of DNA complexes. PEI-CA/pEGFP plasmid DNA complexes were characterized for their size and zeta potential. Gel electrophoresis showed total retardation for PEI-CA/pEGFP complexes formed at weight ratios above 0.25. The particle size and zeta potential of the complexes at a polymer-to-DNA ratio of 0.5 were 295.3 nm and 30.5 mV, respectively. The transfection efficiency of PEI-CA/pEGFP complexes was comparable to unmodified PEI. Cytotoxicity result showed that PEI-CA had lower cytoxicity than PEI. This study suggests that PEI-CA has potential utility as a gene delivery carrier.

Amphiphilic polymers formed from ring-opening polymerization: a strategy for the enhancement of gene delivery

2017 ◽  
Vol 5 (4) ◽  
pp. 718-729 ◽  
Author(s):  
Yi-Mei Zhang ◽  
Zheng Huang ◽  
Ji Zhang ◽  
Wan-Xia Wu ◽  
Yan-Hong Liu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Ring Opening ◽  
Transfection Efficiency ◽  
Ring Opening Polymerization ◽  
Amphiphilic Polymers ◽  
Cationic Lipids ◽  
Promising Strategy

Ring-opening polymerization was found to be a promising strategy to improve the transfection efficiency and serum tolerance of cationic lipids.

Enhanced Transfection Efficiency of Multicomponent Lipoplexes in the Regime of Optimal Membrane Charge Density

2008 ◽  
Vol 112 (36) ◽  
pp. 11298-11304 ◽  
Author(s):  
Giulio Caracciolo ◽  
Daniela Pozzi ◽  
Ruggero Caminiti ◽  
Cristina Marchini ◽  
Maura Montani ◽  
...  
Keyword(s):  
Charge Density ◽  
Transfection Efficiency ◽  
Membrane Charge

CATIONIC POLYMER BASED GENE DELIVERY: UPTAKE AND INTRACELLULAR TRAFFICKING

COSMOS ◽  
2014 ◽  
Vol 10 (01) ◽  
pp. 17-24
Author(s):  
YOONKHEI HO ◽  
HENG-PHON TOO
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Cell Types ◽  
Endosomal Escape ◽  
Current Status ◽  
Uptake Mechanism ◽  
Nuclear Entry ◽  
Dna Complexes ◽  
Major Drawback ◽  
Gene Carriers

To date, low transfection efficiency remains the major drawback of polymer based gene delivery. Many cell types including stem cells, fibroblast and neurons are known to be poorly transfected with polymer based gene carriers and the high toxicity severely restrict their utility in gene delivery. Continual efforts are made to identify cellular barriers to efficient transfection as these carriers have low immunogenicity, ease of manufacturing and scalability. Here, we summarize the current status of understanding on uptake mechanism of polymer-DNA complexes (polyplexes), their endosomal escape, cytosolic transport and nuclear entry of pDNA.

Gene delivery by cationic lipids: in and out of an endosome

2007 ◽  
Vol 35 (1) ◽  
pp. 68-71 ◽  
Author(s):  
D. Hoekstra ◽  
J. Rejman ◽  
L. Wasungu ◽  
F. Shi ◽  
I. Zuhorn
Keyword(s):  
Gene Delivery ◽  
Molecular Mechanisms ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Phase Changes ◽  
Model Systems ◽  
Major Pathway ◽  
Intracellular Lipids ◽  
Relative Contribution ◽  
Endosomal Membranes

Cationic lipids are exploited as vectors (‘lipoplexes’) for delivering nucleic acids, including genes, into cells for both therapeutic and cell biological purposes. However, to meet therapeutic requirements, their efficacy needs major improvement, and better defining the mechanism of entry in relation to eventual transfection efficiency could be part of such a strategy. Endocytosis is the major pathway of entry, but the relative contribution of distinct endocytic pathways, including clathrin- and caveolae-mediated endocytosis and/or macropinocytosis is as yet poorly defined. Escape of DNA/RNA from endosomal compartments is thought to represent a major obstacle. Evidence is accumulating that non-lamellar phase changes of the lipoplexes, facilitated by intracellular lipids, which allow DNA to dissociate from the vector and destabilize endosomal membranes, are instrumental in plasmid translocation into the cytosol, a prerequisite for nuclear delivery. To further clarify molecular mechanisms and to appreciate and overcome intracellular hurdles in lipoplex-mediated gene delivery, quantification of distinct steps in overall transfection and proper model systems are required.

scholarly journals Niosomes based on synthetic cationic lipids for gene delivery: the influence of polar head-groups on the transfection efficiency in HEK-293, ARPE-19 and MSC-D1 cells

2015 ◽  
Vol 13 (4) ◽  
pp. 1068-1081 ◽  
Author(s):  
E. Ojeda ◽  
G. Puras ◽  
M. Agirre ◽  
J. Zárate ◽  
S. Grijalvo ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Head Group ◽  
Polar Head Group ◽  
Hek 293 ◽  
Polar Head ◽  
Head Groups

We designed niosomes based on three lipids that differed only in the polar-head group to analyze their influence on the transfection efficiency.

Novel Poly(Ester Amine) Based on Polycaprolactone and Polyethylenimine as a Gene Carrier: Effect of Hydrophobicity on Transfection Efficiency and Cytotoxicity

2007 ◽  
Vol 342-343 ◽  
pp. 453-456 ◽  
Author(s):  
Rohidas B. Arote ◽  
Tae Hee Kim ◽  
You Kyoung Kim ◽  
Dhananjay Jere ◽  
Hu Lin Jiang ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Carrier ◽  
Particle Sizes ◽  
Dna Complexes ◽  
Novel Gene ◽  
Carrier Effect ◽  
Biodegradable Poly ◽  
Low Cytotoxicity

Novel, biodegradable poly(ester amine)s (PEAs) were synthesized using hydrophobic polycaprolactone diacrylate (PCLDA) and highly cationic polyethylenimine (PEI). This novel gene carrier can form stable DNA complexes with particle sizes around 200 nm, and showing excellent transfection efficiency and relatively low cytotoxicity compared with PEI 25K. Effect of hydrophobicity on transfection efficiency and cytotoxicity was profound and was relatively important parameter for the success of gene delivery.

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