Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Lines and Expression of αvβ3 Integrins in Leiomyoma Cells
2.2. Peptide and Reporter Plasmids
2.3. Preparation of Carrier/DNA Complexes
2.4. DNA Binding and DNAse I Protection Assays
2.5. Size and ʐ-Potential Measurement of Peptide/DNA Complexes
2.6. Transmission Electronic Microscopy
2.7. SYBR-Green Exclusion Assay
2.8. Ellman’s Assay
2.9. Relaxation of Carrier/DNA Complexes by Dextran-Sulfate and DTT Destabilization
2.10. Gene Transfer and Cytotoxicity Assays
2.11. Cellular Uptake of Peptide/DNA Complexes
2.12. Suicide Gene Therapy
2.13. Statistical Analysis
3. Results and Discussion
3.1. Carrier Design
3.2. DNA Binding and DNA Protection Properties of the Carriers
3.3. Kinetics of Carrier/DNA Complexation and Disulfide Bonds Formation during Template Polymerization
3.4. DNA Release after DTT and DS Treatment of the Polyplexes
3.5. Size and ʐ-Potential of the Carrier/DNA Complexes
3.6. Cytotoxicity of DNA-Polyplexes
3.7. Gene Transfer
3.8. Therapeutic Effect of RGD1-R6/pPTK1 Polyplexes after Ganciclovir (GSV) Treatment
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Carrier | Composition (mol%) |
---|---|
RGD0-R6 | RRRRRRRRRHHHH (50 mol%) + CHRRRRRRHC (50 mol%) |
RGD1-R6 | RRRRRRRRRHHHH-CRGDRGPDC (50 mol%) + CHRRRRRRHC (50 mol%) |__________| |
Carrier | Charge Ratio | Size (nm) ± S.D. | ʐ-Potential (mV) ± S.D. |
---|---|---|---|
RGD1-R6 | 4/1 8/1 | 304.8 ± 0.69 98.8 ± 0.49 | 4.7 ± 0.7 16.2 ± 0.1 |
12/1 16/1 | 102.0 ± 0.38 121.2 ± 0.25 | 24.0 ± 0.3 25.2 ± 0.1 | |
RGD0-R6 | 4/1 8/1 | 308.0 ± 0.35 97.5 ± 0.45 | 5.1 ± 0.6 20.2 ± 0.5 |
12/1 16/1 | 101.1 ± 0.51 129.6 ± 0.42 | 25.1 ± 0.5 26.9 ± 0.2 |
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Egorova, A.; Shtykalova, S.; Selutin, A.; Shved, N.; Maretina, M.; Selkov, S.; Baranov, V.; Kiselev, A. Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma. Pharmaceutics 2021, 13, 202. https://doi.org/10.3390/pharmaceutics13020202
Egorova A, Shtykalova S, Selutin A, Shved N, Maretina M, Selkov S, Baranov V, Kiselev A. Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma. Pharmaceutics. 2021; 13(2):202. https://doi.org/10.3390/pharmaceutics13020202
Chicago/Turabian StyleEgorova, Anna, Sofia Shtykalova, Alexander Selutin, Natalia Shved, Marianna Maretina, Sergei Selkov, Vladislav Baranov, and Anton Kiselev. 2021. "Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma" Pharmaceutics 13, no. 2: 202. https://doi.org/10.3390/pharmaceutics13020202
APA StyleEgorova, A., Shtykalova, S., Selutin, A., Shved, N., Maretina, M., Selkov, S., Baranov, V., & Kiselev, A. (2021). Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma. Pharmaceutics, 13(2), 202. https://doi.org/10.3390/pharmaceutics13020202