Lysine dendrimers as vectors for delivery of genetic constructs to eukaryotic cells

Kiselev, Anton; Ilina, Polina; Egorova, Anna; Baranov, A. N.; Guryanov, Ivan; Bayanova, N. V.; Tarasenko, I. I.; Lesina, E. A.; Vlasov, G. P.; Baranov, Vladislav S

doi:10.1134/s1022795407060014

Cited by 17 publications

(13 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Peptide-binding to DNA was monitored using the ethidium bromide (EtBr) fluorescence quenching method as described previously [ 48 ]. Peptide binding to siRNA was studied with the SYBR-Green fluorescence quenching method [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

Characterization of iRGD-Ligand Modified Arginine-Histidine-Rich Peptides for Nucleic Acid Therapeutics Delivery to αvβ3 Integrin-Expressing Cancer Cells

et al. 2020

View full text Add to dashboard Cite

Efficient and specific delivery of nucleic acid (NA) therapeutics to tumor cells is extremely important for cancer gene therapy. Various therapeutic strategies include delivery of DNA-therapeutics such as immunostimulatory or suicide genes and delivery of siRNA-therapeutics able to silence expression of cancer-related genes. Peptides are a promising class of non-viral vehicles which are biodegradable and can efficiently condense, protect and specifically deliver NA to the cells. Here we designed arginine-histidine-rich peptide carriers consisting of an iRGD ligand to target αvβ3 integrins and studied them as vehicles for DNA and siRNA delivery to cancer cells. Combination of iRGD-modified and unmodified arginine–histidine-rich peptides during NA complexation resulted in carriers with different ligand contents. The NA-binding and protecting properties in vitro transfection efficiency and cytotoxicity of the DNA- and siRNA-polyplexes were studied and the most efficient carrier RGD1 was determined. The ability of the peptides to mediate specific intracellular uptake was confirmed inhuman cervical carcinoma (HeLa), human kidney (293T) and human pancreatic (PANC-1) cell lines with different αvβ3 integrins surface expression. By means of RGD1 carrier, efficient delivery of the herpes simplex virus (HSV-1) thymidine kinase gene to PANC-1 cells was demonstrated. Subsequent ganciclovir treatment led to a reduction of PANC-1 cells’ viability by up to 54%. Efficient RNAi-mediated down-regulation of GFP and VEGFA gene expression was achieved in MDA-MB-231-GFP+ breast cancer and EA.hy926 endothelial cells, respectively, by means of RGD1/siRNA polyplexes. Here we demonstrated that the peptide carrier RGD1 can be considered as promising candidate for development of NA therapeutics delivery systems useful in cancer gene therapy.

show abstract

Section: Methodsmentioning

confidence: 99%

Characterization of iRGD-Ligand Modified Arginine-Histidine-Rich Peptides for Nucleic Acid Therapeutics Delivery to αvβ3 Integrin-Expressing Cancer Cells

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Then, combiMAG MNPs were added to the DNA/peptide complex suspension according to the manufacturer's recommendations and the suspension was incubated for 15 min at room temperature. DNA binding was evaluated by ethidium bromide displacement [24].…”

Section: Formation Of R6p-crgd/dna/mnps Polyplexesmentioning

confidence: 99%

Magnetic Nanoparticles as a Component of Peptide-Based DNA Delivery System for Suicide Gene Therapy of Uterine Leiomyoma

et al. 2022

View full text Add to dashboard Cite

Suicidegene therapy is considered a promising approach for the treatment of uterine leiomyoma (UL), a benign tumor in women characterized by precise localization. In this study, we investigate the efficiency of αvβ3 integrin-targeted arginine-rich peptide carrier R6p-cRGD electrostatically bound to magnetic nanoparticles (MNPs) for targeted DNA delivery into the UL cells. The physico–chemical and cytotoxic properties, transfection efficiency, and specificity of R6p-cRGD/DNA/MNPs polyplexes were evaluated. The addition of MNPs resulted in a decrease in the time needed for successful transfection with simultaneous increase in efficiency. We revealed a therapeutic effect on primary UL cells after delivery of plasmid encoding the herpes simplex virus type 1 (HSV-1) thymidine kinase gene. Treatment with ganciclovir resulted in 20% efficiency of suicide gene therapy in UL cells transfected with the pPTK-1 plasmid. Based on these results, we conclude that the use of cationic peptide carriers with MNPs can be promising for the development of modular non-viral carriers for suicide gene delivery to UL cells.

show abstract

“…are considered to be promising with respect to the development of ‘artificial viruses’, equalling viral counterparts in terms of their transfection efficacy, at the same time as being much safer, target‐cell specific, non‐immunogenic and relatively inexpensive to prepare at scales that permit their clinical use . Common synthetic polycations, which have been developed and studied for nucleic acid (NA) delivery, are based on polyethylenimine, polyamidoamine dendrimers, lysine‐containing polypeptides and dendrimers . The transfection efficiency of the NA‐polycation complexes, termed polyplexes, strongly depends on their ability to condense and protect NA from degradation by nucleases, as well as to provide specific cellular access and intracellular distribution of the polyplexes.…”

Section: Introductionmentioning

confidence: 99%

Development of a receptor-targeted gene delivery system using CXCR4 ligand-conjugated cross-linking peptides

et al. 2014

View full text Add to dashboard Cite

show abstract

Lysine dendrimers as vectors for delivery of genetic constructs to eukaryotic cells

Cited by 17 publications

References 22 publications

Characterization of iRGD-Ligand Modified Arginine-Histidine-Rich Peptides for Nucleic Acid Therapeutics Delivery to αvβ3 Integrin-Expressing Cancer Cells

Characterization of iRGD-Ligand Modified Arginine-Histidine-Rich Peptides for Nucleic Acid Therapeutics Delivery to αvβ3 Integrin-Expressing Cancer Cells

Magnetic Nanoparticles as a Component of Peptide-Based DNA Delivery System for Suicide Gene Therapy of Uterine Leiomyoma

Development of a receptor-targeted gene delivery system using CXCR4 ligand-conjugated cross-linking peptides

Contact Info

Product

Resources

About