4.6 Article

Chemico-Physical Properties of Some 1,1′-Bis-alkyl-2,2′-hexane-1,6-diyl-bispyridinium Chlorides Hydrogenated and Partially Fluorinated for Gene Delivery

Journal

MOLECULES
Volume 28, Issue 8, Pages -

Publisher

MDPI
DOI: 10.3390/molecules28083585

Keywords

heterocyclic gemini cationic surfactants; non-viral vectors; gene delivery; partially fluorinated gemini surfactants; atomic force microscopy on DNA; DNA-surfactant interaction; DNA circular dichroism spectra; ellipsometry

Ask authors/readers for more resources

The development of efficient and safe non-viral vectors is crucial for gene-based medicine. This study shows that the length of the hydrophobic chain does not significantly affect gene delivery, while the length of the spacer plays a key role in gene transfer capacity.
The development of very efficient and safe non-viral vectors, constituted mainly by cationic lipids bearing multiple charges, is a landmark for in vivo gene-based medicine. To understand the effect of the hydrophobic chain's length, we here report the synthesis, and the chemico-physical and biological characterization, of a new term of the homologous series of hydrogenated gemini bispyridinium surfactants, the 1,1 '-bis-dodecyl-2,2 '-hexane-1,6-diyl-bispyridinium chloride (GP12_6). Moreover, we have collected and compared the thermodynamic micellization parameters (cmc, changes in enthalpy, free energy, and entropy of micellization) obtained by isothermal titration calorimetry (ITC) experiments for hydrogenated surfactants GP12_6 and GP16_6, and for the partially fluorinated ones, FGPn (where n is the spacer length). The data obtained for GP12_6 by EMSA, MTT, transient transfection assays, and AFM imaging show that in this class of compounds, the gene delivery ability strictly depends on the spacer length but barely on the hydrophobic tail length. CD spectra have been shown to be a useful tool to verify the formation of lipoplexes due to the presence of a tail in the 288-320 nm region attributed to a chiroptical feature named psi-phase. Ellipsometric measurements suggest that FGP6 and FGP8 (showing a very interesting gene delivery activity, when formulated with DOPE) act in a very similar way, and dissimilar from FGP4, exactly as in the case of transfection, and confirm the hypothesis suggested by previously obtained thermodynamic data about the requirement of a proper length of the spacer to allow the molecule to form a sort of molecular tong able to intercalate DNA.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available