Nonviral Gene Delivery: Gemini Bispyridinium Surfactant-Based DNA Nanoparticles
| Autor: | Gaetano Donofrio, F. Bacciottini, Carlotta Compari, Bożenna Różycka-Roszak, Pierluigi Quagliotto, Francesco Sansone, Paweł Misiak, Nadia Barbero, Emilia Fisicaro, Laura Contardi, Guido Viscardi, Edyta Woźniak |
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| Rok vydání: | 2014 |
| Předmět: |
Stereochemistry
Electrophoretic Mobility Shift Assay Pyridinium Compounds Gene delivery Microscopy Atomic Force Transfection AQUEOUS-SOLUTIONS PHOSPHATIDYLCHOLINE BILAYERS TRANSFECTION PROPERTIES BIOLOGICAL-PROPERTIES CATIONIC SURFACTANTS VECTORS CONDENSATION COMPLEXES BEHAVIOR AGGREGATION Surface-Active Agents chemistry.chemical_compound Homologous series Cell Line Tumor Materials Chemistry Humans Physical and Theoretical Chemistry Alkyl chemistry.chemical_classification Aqueous solution Calorimetry Differential Scanning Cationic polymerization DNA Combinatorial chemistry Surfaces Coatings and Films Electrophoresis chemistry Nanoparticles Thermodynamics Pyridinium Plasmids |
| Zdroj: | The Journal of Physical Chemistry B. 118:13183-13191 |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/jp507999g |
| Popis: | The interaction with a model membrane, the formation of DNA nanoparticles, and the transfection ability of a homologous series of bispyridinium dihexadecyl cationic gemini surfactants, differing in the length of the alkyl spacer bridging the two pyridinium polar heads in the 1 and 1' positions (P16-n with n = 3, 4, 8, 12), have been studied by means of differential scanning calorimetry (DSC), atomic force microscopy, electrophoresis mobility shift assay, and transient transfection assay measurements. The results presented here show that their performance in gene delivery is strictly related to their structure in solution. For the first time the different transfection activities of the compounds can be explained by referring to their thermodynamic properties in solution, previously studied. The compound with a spacer formed by four carbon atoms, showing unexpected enthalpic properties vs concentration in solution, is the only one giving rise to a transfection activity comparable to that of the commercial reagent, when formulated with L-α-dioleoylphosphatidylethanolamine. We suggest that P16-4 behaves like molecular tongs able to grip basic groups near each other, allowing the formation of compact and nearly spherical DNA particles. The compound with the longest spacer gives rise to loosely condensed structures by forming a sort of bow, not able to give rise to transfection notwithstanding the double positive charge of the molecule. On the other hand, DSC measurements on synthetic membranes show that the compounds with the shortest spacers (three and four methylene groups) practically do not interact with the 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine membrane, while compounds P16-8 and, particularly, P16-12 induce the formation of surfactant-rich and surfactant-poor domains in the membrane, without showing any peculiarity for compound P16-4. This could suggest that the mechanisms involved in the interaction with the model membrane and in gene delivery are substantially different and could strike a blow for an endocytosis mechanism for the internalization in the cell of the DNA nanoparticles. |
| Databáze: | OpenAIRE |
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