The Process of Binding and Releasing of Genetic Material from Lipoplexes Based on Trimeric Surfactants and Phospholipids
Abstract
:1. Introduction
2. Results
2.1. Binding and Releasing of Nucleic Acid
2.2. The Conformation of Nucleic Acid
2.3. The Cytotoxicity Tests
2.4. Topographic AFM Studies
3. Discussion
4. Materials and Methods
4.1. Cationic Trimeric Surfactants
4.2. Lipoplex Preparation
4.3. Electrophoretic Tests
4.4. Cytotoxicity Tests
4.4.1. Cell Culture
4.4.2. Cytotoxicity Tests
4.4.3. MTT Cell Viability Assay
4.4.4. Trypan Blue Staining
4.5. Circular Dichroism Spectroscopy
4.6. Atomic Force Microscopy
5. Conclusions
6. Patents
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Lundstrom, K. Viral Vectors in Gene Therapy. Diseases 2018, 6, 42. [Google Scholar] [CrossRef] [Green Version]
- Lee, C.S.; Bishop, E.S.; Zhang, R.; Yu, X.; Farina, E.M.; Yan, S.; Zhao, C.; Zeng, Z.; Shu, Y.; Wu, X.; et al. Adenovirus-Mediated Gene Delivery: Potential Applications for Gene and Cell-Based Therapies in the New Era of Personalized Medicine. Genes Dis. 2017, 4, 43–63. [Google Scholar] [CrossRef]
- Jayant, R.D.; Sosa, D.; Kaushik, A.; Atluri, V.; Vashist, A.; Tomitaka, A.; Nair, M. Current Status of Non-Viral Gene Therapy for CNS Disorders. Expert Opin. Drug Deliv. 2016, 13, 1433–1445. [Google Scholar] [CrossRef] [Green Version]
- Sum, C.H.; Nafissi, N.; Slavcev, R.A.; Wettig, S. Physical Characterization of Gemini Surfactant-Based Synthetic Vectors for the Delivery of Linear Covalently Closed (LCC) DNA Ministrings. PLoS ONE 2015, 10, e0142875. [Google Scholar] [CrossRef] [PubMed]
- Bozzuto, G.; Molinari, A. Liposomes as Nanomedical Devices. Int. J. Nanomed. 2015, 975–999. [Google Scholar] [CrossRef] [Green Version]
- Ahmed, T.; Kamel, A.O.; Wettig, S.D. Interactions between DNA and Gemini Surfactant: Impact on Gene Therapy: Part I. Nanomedicine 2016, 11, 289–306. [Google Scholar] [CrossRef] [PubMed]
- Ahmed, T.; Kamel, A.O.; Wettig, S.D. Interactions between DNA and Gemini Surfactant: Impact on Gene Therapy: Part II. Nanomedicine 2016, 11, 403–420. [Google Scholar] [CrossRef]
- Bombelli, C.; Giansanti, L.; Luciani, P.; Mancini, G. Gemini Surfactant Based Carriers in Gene and Drug Delivery. Curr. Med. Chem. 2009, 16, 171–183. [Google Scholar] [CrossRef] [PubMed]
- Muñoz-Úbeda, M.; Misra, S.K.; Barrán-Berdón, A.L.; Datta, S.; Aicart-Ramos, C.; Castro-Hartmann, P.; Kondaiah, P.; Junquera, E.; Bhattacharya, S.; Aicart, E. How Does the Spacer Length of Cationic Gemini Lipids Influence the Lipoplex Formation with Plasmid DNA? Physicochemical and Biochemical Characterizations and Their Relevance in Gene Therapy. Biomacromolecules 2012, 13, 3926–3937. [Google Scholar] [CrossRef]
- Sharma, V.D.; Lees, J.; Hoffman, N.E.; Brailoiu, E.; Madesh, M.; Wunder, S.L.; Ilies, M.A. Modulation of Pyridinium Cationic Lipid-DNA Complex Properties by Pyridinium Gemini Surfactants and Its Impact on Lipoplex Transfection Properties. Mol. Pharm. 2014, 11, 545–559. [Google Scholar] [CrossRef] [Green Version]
- Martínez-Negro, M.; Blanco-Fernández, L.; Tentori, P.; Pérez, L.; Pinazo, A.; Tros de Ilarduya, C.; Aicart, E.; Junquera, E. A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study. Nanomaterials 2018, 8, 1061. [Google Scholar] [CrossRef] [Green Version]
- Pietralik, Z.; Kołodziejska, Ż.; Weiss, M.; Kozak, M. Gemini Surfactants Based on Bis-Imidazolium Alkoxy Derivatives as Effective Agents for Delivery of Nucleic Acids: A Structural and Spectroscopic Study. PLoS ONE 2015, 10, e0144373. [Google Scholar] [CrossRef] [PubMed]
- Wani, F.A.; Amaduddin; Aneja, B.; Sheehan, G.; Kavanagh, K.; Ahmad, R.; Abid, M.; Patel, R. Synthesis of Novel Benzimidazolium Gemini Surfactants and Evaluation of Their Anti-Candida Activity. ACS Omega 2019, 4, 11871–11879. [Google Scholar] [CrossRef] [PubMed]
- Al-Dulaymi, M.; Mohammed-Saeid, W.; El-Aneed, A.; Badea, I. Peptide-Modified Gemini Surfactants: Preparation and Characterization for Gene Delivery. In Pharmaceutical Nanotechnology; Methods in Molecular Biology; Weissig, V., Elbayoumi, T., Eds.; Springer New York: New York, NY, USA, 2019; Volume 2000, pp. 203–225. ISBN 978-1-4939-9515-8. [Google Scholar]
- Andrzejewska, W.; Wilkowska, M.; Skrzypczak, A.; Kozak, M. Ammonium Gemini Surfactants Form Complexes with Model Oligomers of siRNA and dsDNA. Int. J. Mol. Sci. 2019, 20, 5546. [Google Scholar] [CrossRef] [Green Version]
- Pietralik, Z.; Kumita, J.R.; Dobson, C.M.; Kozak, M. The Influence of Novel Gemini Surfactants Containing Cycloalkyl Side-Chains on the Structural Phases of DNA in Solution. Colloids Surf. B 2015, 131, 83–92. [Google Scholar] [CrossRef] [PubMed]
- Pietralik, Z.; Skrzypczak, A.; Kozak, M. Dicationic Surfactants with Glycine Counter Ions for Oligonucleotide Transportation. ChemPhysChem 2016, 17, 2424–2433. [Google Scholar] [CrossRef]
- Kypr, J.; Kejnovska, I.; Renciuk, D.; Vorlickova, M. Circular Dichroism and Conformational Polymorphism of DNA. Nucleic Acids Res. 2009, 37, 1713–1725. [Google Scholar] [CrossRef] [Green Version]
- Zhao, X.; Shang, Y.; Liu, H.; Hu, Y.; Jiang, J. Interaction of DNA with Cationic Gemini Surfactant Trimethylene-1,3-Bis (Dodecyldimethyl-Ammonium Bromide) and Anionic Surfactant SDS Mixed System. Chin. J. Chem. Eng. 2008, 16, 923–928. [Google Scholar] [CrossRef]
- Andrzejewska, W.; Wilkowska, M.; Peplińska, B.; Skrzypczak, A.; Kozak, M. Structural Characterization of Transfection Nanosystems Based on Tricationic Surfactants and Short Double Stranded Oligonucleotides. Biochem. Biophys. Res. Commun. 2019, 518, 706–711. [Google Scholar] [CrossRef]
- Donkuru, M.; Badea, I.; Wettig, S.; Verrall, R.; Elsabahy, M.; Foldvari, M. Advancing Nonviral Gene Delivery: Lipid- and Surfactant-Based Nanoparticle Design Strategies. Nanomedicine 2010, 5, 1103–1127. [Google Scholar] [CrossRef] [PubMed]
- Gomes-da-Silva, L.C.; Fonseca, N.A.; Moura, V.; Pedroso de Lima, M.C.; Simões, S.; Moreira, J.N. Lipid-Based Nanoparticles for SiRNA Delivery in Cancer Therapy: Paradigms and Challenges. Acc. Chem. Res. 2012, 45, 1163–1171. [Google Scholar] [CrossRef] [PubMed]
- Barba, A.A.; Bochicchio, S.; Dalmoro, A.; Lamberti, G. Lipid Delivery Systems for Nucleic-Acid-Based-Drugs: From Production to Clinical Applications. Pharmaceutics 2019, 11, 360. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pardi, N.; Hogan, M.J.; Porter, F.W.; Weissman, D. MRNA Vaccines—A New Era in Vaccinology. Nat. Rev. Drug Discov. 2018, 17, 261–279. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Reichmuth, A.M.; Oberli, M.A.; Jaklenec, A.; Langer, R.; Blankschtein, D. MRNA Vaccine Delivery Using Lipid Nanoparticles. Ther Deliv. 2016, 7, 319–334. [Google Scholar] [CrossRef] [Green Version]
- Semple, S.C.; Akinc, A.; Chen, J.; Sandhu, A.P.; Mui, B.L.; Cho, C.K.; Sah, D.W.Y.; Stebbing, D.; Crosley, E.J.; Yaworski, E.; et al. Rational Design of Cationic Lipids for SiRNA Delivery. Nat. Biotechnol. 2010, 28, 172–176. [Google Scholar] [CrossRef] [PubMed]
- Movahedi, F.; Hu, R.G.; Becker, D.L.; Xu, C. Stimuli-Responsive Liposomes for the Delivery of Nucleic Acid Therapeutics. Nanomedicine 2015, 11, 1575–1584. [Google Scholar] [CrossRef] [PubMed]
- Cullis, P.R.; Chonn, A.; Semple, S.C. Interactions of Liposomes and Lipid-Based Carrier Systems with Blood Proteins: Relation to Clearance Behaviour in Vivo. Adv. Drug Deliv. Rev. 1998, 32, 3–17. [Google Scholar] [CrossRef]
- Sercombe, L.; Veerati, T.; Moheimani, F.; Wu, S.Y.; Sood, A.K.; Hua, S. Advances and Challenges of Liposome Assisted Drug Delivery. Front. Pharmacol. 2015, 6. [Google Scholar] [CrossRef] [Green Version]
- Muñoz-Úbeda, M.; Misra, S.K.; Barrán-Berdón, A.L.; Aicart-Ramos, C.; Sierra, M.B.; Biswas, J.; Kondaiah, P.; Junquera, E.; Bhattacharya, S.; Aicart, E. Why Is Less Cationic Lipid Required to Prepare Lipoplexes from Plasmid DNA than Linear DNA in Gene Therapy? J. Am. Chem. Soc. 2011, 133, 18014–18017. [Google Scholar] [CrossRef]
- Andrzejewska, W.; Wilkowska, M.; Chrabąszczewska, M.; Kozak, M. The Study of Complexation between Dicationic Surfactants and the DNA Duplex Using Structural and Spectroscopic Methods. RSC Adv. 2017, 7, 26006–26018. [Google Scholar] [CrossRef] [Green Version]
- Kirby, A.J.; Camilleri, P.; Engberts, J.B.F.N.; Feiters, M.C.; Nolte, R.J.M.; Söderman, O.; Bergsma, M.; Bell, P.C.; Fielden, M.L.; García Rodríguez, C.L.; et al. Gemini Surfactants: New Synthetic Vectors for Gene Transfection. Angew. Chem. Int. Ed. Engl. 2003, 42, 1448–1457. [Google Scholar] [CrossRef]
- Wang, H.; Kaur, T.; Tavakoli, N.; Joseph, J.; Wettig, S. Transfection and Structural Properties of Phytanyl Substituted Gemini Surfactant-Based Vectors for Gene Delivery. Phys. Chem. Chem. Phys. 2013, 15, 20510. [Google Scholar] [CrossRef]
- Laschewsky, A.; Wattebled, L.; Arotçaréna, M.; Habib-Jiwan, J.-L.; Rakotoaly, R.H. Synthesis and Properties of Cationic Oligomeric Surfactants. Langmuir 2005, 21, 7170–7179. [Google Scholar] [CrossRef] [PubMed]
- Murguía, M.C.; Cabrera, M.I.; Guastavino, J.F.; Grau, R.J. New Oligomeric Surfactants with Multiple-Ring Spacers: Synthesis and Tensioactive Properties. Colloids Surf. A 2005, 262, 1–7. [Google Scholar] [CrossRef]
- Strober, W. Trypan Blue Exclusion Test of Cell Viability. Curr. Protoc. Immunol. 2015, 111. [Google Scholar] [CrossRef]
- Xing, H.; Lu, M.; Yang, T.; Liu, H.; Sun, Y.; Zhao, X.; Xu, H.; Yang, L.; Ding, P. Structure-Function Relationships of Nonviral Gene Vectors: Lessons from Antimicrobial Polymers. Acta Biomater. 2019, 86, 15–40. [Google Scholar] [CrossRef] [PubMed]
- Garcia, M.T.; Ribosa, I.; Kowalczyk, I.; Pakiet, M.; Brycki, B. Biodegradability and Aquatic Toxicity of New Cleavable Betainate Cationic Oligomeric Surfactants. J. Hazard. Mater. 2019, 371, 108–114. [Google Scholar] [CrossRef] [PubMed]
- Hansen, F.Y.; Peters, G.H.; Taub, H.; Miskowiec, A. Diffusion of Water and Selected Atoms in DMPC Lipid Bilayer Membranes. J. Chem. Phys. 2012, 137, 204910. [Google Scholar] [CrossRef] [Green Version]
- Abedi Karjiban, R.; Shaari, N.S.; Gunasakaran, U.V.; Basri, M. A Coarse-Grained Molecular Dynamics Study of DLPC, DMPC, DPPC, and DSPC Mixtures in Aqueous Solution. J. Chem. 2013, 2013, 1–6. [Google Scholar] [CrossRef] [Green Version]
- Godbey, W.T. Gene Delivery. In An Introduction to Biotechnology; Godbey, W.T., Ed.; Academic Press Inc.: London, UK, 2014; pp. 275–312. ISBN 978-1-907568-28-2. [Google Scholar]
- Zuhorn, I.S.; Bakowsky, U.; Polushkin, E.; Visser, W.H.; Stuart, M.C.A.; Engberts, J.B.F.N.; Hoekstra, D. Nonbilayer Phase of Lipoplex-Membrane Mixture Determines Endosomal Escape of Genetic Cargo and Transfection Efficiency. Mol. Ther. 2005, 11, 801–810. [Google Scholar] [CrossRef] [Green Version]
- Dong, C.; Badea, I.; Poorghorban, M.; Verrall, R.; Foldvari, M. Impact of Phospholipids on Plasmid Packaging and Toxicity of Gemini Nanoparticles. J. Mater. Chem. B 2015, 3, 8806–8822. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Adamcik, J.; Klinov, D.V.; Witz, G.; Sekatskii, S.K.; Dietler, G. Observation of Single-Stranded DNA on Mica and Highly Oriented Pyrolytic Graphite by Atomic Force Microscopy. FEBS Lett. 2006, 580, 5671–5675. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Belletti, D.; Tonelli, M.; Forni, F.; Tosi, G.; Vandelli, M.A.; Ruozi, B. AFM and TEM Characterization of SiRNAs Lipoplexes: A Combinatory Tools to Predict the Efficacy of Complexation. Colloids Surf. A 2013, 436, 459–466. [Google Scholar] [CrossRef]
- Ma, B.; Zhang, S.; Jiang, H.; Zhao, B.; Lv, H. Lipoplex Morphologies and Their Influences on Transfection Efficiency in Gene Delivery. J. Control. Release 2007, 123, 184–194. [Google Scholar] [CrossRef]
- Tarahovsky, Y.S.; Rakhmanova, V.A.; Epand, R.M.; MacDonald, R.C. High Temperature Stabilization of DNA in Complexes with Cationic Lipids. Biophys. J. 2002, 82, 264–273. [Google Scholar] [CrossRef] [Green Version]
- Koynova, R.; Tarahovsky, Y.S.; Wang, L.; MacDonald, R.C. Lipoplex Formulation of Superior Efficacy Exhibits High Surface Activity and Fusogenicity, and Readily Releases DNA. Biochim. Biophys. Acta 2007, 1768, 375–386. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kumar, K.; Barrán-Berdón, A.L.; Datta, S.; Muñoz-Úbeda, M.; Aicart-Ramos, C.; Kondaiah, P.; Junquera, E.; Bhattacharya, S.; Aicart, E. A Delocalizable Cationic Headgroup Together with an Oligo-Oxyethylene Spacer in Gemini Cationic Lipids Improves Their Biological Activity as Vectors of Plasmid DNA. J. Mater. Chem. B 2015, 3, 1495–1506. [Google Scholar] [CrossRef] [PubMed]
- Troiber, C.; Kasper, J.C.; Milani, S.; Scheible, M.; Martin, I.; Schaubhut, F.; Küchler, S.; Rädler, J.; Simmel, F.C.; Friess, W.; et al. Comparison of Four Different Particle Sizing Methods for SiRNA Polyplex Characterization. Eur. J. Pharm. Biopharm. 2013, 84, 255–264. [Google Scholar] [CrossRef]
- Dan, N. Lipid-Nucleic Acid Supramolecular Complexes: Lipoplex Structure and the Kinetics of Formation. AIMS Biophys. 2015, 2, 163–183. [Google Scholar] [CrossRef]
- Zhou, T.; Xu, G.; Ao, M.; Yang, Y.; Wang, C. DNA Compaction to Multi-Molecular DNA Condensation Induced by Cationic Imidazolium Gemini Surfactants. Colloids Surf. A 2012, 414, 33–40. [Google Scholar] [CrossRef]
- Faizullin, D.A.; Zuev, Y.F.; Zakharova, L.Y.; Pokrovsky, A.G.; Korobeinikov, V.A.; Mukhametzyanov, T.A.; Konovalov, A.I. Lipoplexes of Dicationic Gemini Surfactants with DNA: Structural Features of DNA Compaction and Transfection Efficiency. In Doklady Biochemistry and Biophysics; Pleiades Publishing: New York, NY, USA, 2015; Volume 465, pp. 432–435. [Google Scholar] [CrossRef]
- Braun, C.S.; Kueltzo, L.A.; Middaugh, C.R. Ultraviolet Absorption and Circular Dichroism Spectroscopy of Nonviral Gene Delivery Complexes. In Nonviral Vectors for Gene Therapy; Humana Press: Totova, NJ, USA, 2001; Volume 65, pp. 253–284. ISBN 978-1-59259-139-8. [Google Scholar]
- Zhao, X.; Shang, Y.; Hu, J.; Liu, H.; Hu, Y. Biophysical Characterization of Complexation of DNA with Oppositely Charged Gemini Surfactant 12-3-12. Biophys. Chem. 2008, 138, 144–149. [Google Scholar] [CrossRef] [PubMed]
- Pernak, J.; Skrzypczak, A.; Lota, G.; Frackowiak, E. Synthesis and Properties of Trigeminal Tricationic Ionic Liquids. Chem. Eur. J. 2007, 13, 3106–3112. [Google Scholar] [CrossRef] [PubMed]
- Emel’yanenko, V.N.; Portnova, S.V.; Verevkin, S.P.; Skrzypczak, A.; Schubert, T. Building Blocks for Ionic Liquids: Vapor Pressures and Vaporization Enthalpies of 1-(n-Alkyl)-Imidazoles. J. Chem. Thermodyn. 2011, 43, 1500–1505. [Google Scholar] [CrossRef]
- Nečas, D.; Klapetek, P. Gwyddion: An Open-Source Software for SPM Data Analysis. Open Phys. 2012, 10, 181–188. [Google Scholar] [CrossRef]
DNA. | Lipids/Surfactant | TRI_N | TRI_IMI | TRI_BEN |
---|---|---|---|---|
20 kbp | - | 4 | 5 | 14 |
L1 | 2 | 2 | 4 | |
L2 | 1 | 1 | 2 | |
L3 | 0.75 | 2 | 4 | |
185 bp | - | 4 | 5 | 16 |
L1 | 2 | 2 | 14 | |
L2 | 3 | 3 | 10 | |
L3 | 3 | 2 | 10 | |
21 bp | - | 8 | 8 | 18 |
L1 | 6 | 6 | 16 | |
L2 | 5 | 6 | 16 | |
L3 | 6 | 6 | 16 |
Complex. | Heparin Concentration during Release (µg/mL) | ||||
---|---|---|---|---|---|
Surfactant | p/n | - | L1 | L2 | L3 |
TRI_N | 5 | 2.5 | 10 | 10 | 10 |
10 | 2.5 | 10 | 10 | 10 | |
20 | 10 | 25 | 25 | 25 | |
TRI_IMI | 5 | 2.5 | 10 | 10 | 10 |
10 | 2.5 | 10 | 10 | 10 | |
20 | 10 | 25 | 25 | 10 | |
TRI_BEN | 10 | - | 2.5 | 2.5 | 2.5 |
20 | 1 | 10 | 10 | 10 |
Surfactant | Lipids | EC50 (µM) |
---|---|---|
TRI_N | - | 15 ± 3 |
L1 | 762 ± 12 | |
L2 | 856 ± 24 | |
L3 | 302 ± 6 | |
TRI_IMI | - | 24 ± 6 |
L1 | 723 ± 15 | |
L2 | 962 ± 18 | |
L3 | 578 ± 12 | |
TRI_BEN | - | 60 ± 12 |
L1 | 526 ± 21 | |
L2 | 648 ± 24 | |
L3 | 294 ± 15 |
System | Surfactant Concentration (µM) | |||||||
---|---|---|---|---|---|---|---|---|
0 | 4 | 30 | 60 | 100 | 500 | 1000 | 2000 | |
TRI_N | x | x | x | x | x | x | x | |
TRI_IMI | x | x | x | x | x | x | x | |
TRI_BEN | x | x | x | x | x | x | ||
Surfactants and lipids | x | x | x | x |
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Polańska, Ż.; Pietralik-Molińska, Z.; Wojciechowska, D.; Moliński, A.; Weiss, M.; Skrzypczak, A.; Kozak, M. The Process of Binding and Releasing of Genetic Material from Lipoplexes Based on Trimeric Surfactants and Phospholipids. Int. J. Mol. Sci. 2021, 22, 7744. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147744
Polańska Ż, Pietralik-Molińska Z, Wojciechowska D, Moliński A, Weiss M, Skrzypczak A, Kozak M. The Process of Binding and Releasing of Genetic Material from Lipoplexes Based on Trimeric Surfactants and Phospholipids. International Journal of Molecular Sciences. 2021; 22(14):7744. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147744
Chicago/Turabian StylePolańska, Żaneta, Zuzanna Pietralik-Molińska, Daria Wojciechowska, Augustyn Moliński, Marek Weiss, Andrzej Skrzypczak, and Maciej Kozak. 2021. "The Process of Binding and Releasing of Genetic Material from Lipoplexes Based on Trimeric Surfactants and Phospholipids" International Journal of Molecular Sciences 22, no. 14: 7744. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147744