Fusion of gemini based cationic liposomes with cell membrane models: implications for their biological activity

Aleandri, Simone; Bombelli, Cecilia; Bonicelli, M.G.; Bordi, F.; Giansanti, Luisa; Mancini, Giovanna; Ierino, Marco; Sennato, Simona

doi:10.1016/j.bbamem.2012.10.001

Cited by 30 publications

(13 citation statements)

References 34 publications

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“…The determined ζ-potential of the zwitterionic DMPC LUVs was as expected close to zero. 32 In the presence of MSI-78(4−20) or MSI-78, the ζ-potential remains nearly unchanged (Figure 2A). The addition of increased concentrations of either peptide to DMPC LUVs caused almost no alteration on the zeta potential values, suggesting a weak interaction or non-interaction with the mammalian membrane model.…”

Section: Molecular Pharmaceuticsmentioning

confidence: 99%

A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells

et al. 2015

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Antimicrobial peptides are widely recognized as an excellent alternative to conventional antibiotics. MSI-78, a highly effective and broad spectrum AMP, is one of the most promising AMPs for clinical application. In this study, we have designed shorter derivatives of MSI-78 with the aim of improving selectivity while maintaining antimicrobial activity. Shorter 17-mer derivatives were created by truncating MSI-78 at the N-and/or C-termini, while spanning MSI-78 sequence. Despite the truncations made, we found a 17-mer peptide, MSI-78(4−20) (KFLKKAKKFGKAFVKIL), which was demonstrated to be as effective as MSI-78 against the Gram-positive Staphylococcus strains tested and the Gram-negative Pseudomonas aeruginosa. This shorter derivative is more selective toward bacterial cells as it was less toxic to erythrocytes than MSI-78, representing an improved version of the lead peptide. Biophysical studies support a mechanism of action for based on the disruption of the bacterial membrane permeability barrier, which in turn leads to loss of membrane integrity and ultimately to cell death. These features point to a mechanism of action similar to the one described for the lead peptide MSI-78.

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Section: Molecular Pharmaceuticsmentioning

confidence: 99%

A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells

et al. 2015

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“…Gemini QAS have much lower CMC (critical micelle concentrations) in comparison to monomeric surfactants [3]. Gemini QAS surfactants are able to form bilayer aggregates, like liposomes, and are extensively studied as potential non-viral gene delivery systems or drug carriers [4][5][6]. The activity of gemini QAS against microorganisms is generally stronger in comparison to the corresponding monomeric compounds and depends on the structure of the gemini molecule [7].…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Activity of Alanine‐Derived Gemini Quaternary Ammonium Compounds

Piecuch

Obłąk

Guz-Regner

2015

J Surfact & Detergents

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The antibacterial activity of alanine-derived gemini quaternary ammonium salts (chlorides and bromides) with various spacer and alkyl chain lengths was investigated. The studied compounds exhibited a strong bactericidal effect, especially bromides with 10 and 12 carbon alkyl chains and 3 carbon spacer groups (TMPAL-10 Br and TMPAL-12 Br), with a short contact time. Both salts dislodged biofilms of Pseudomonas aeruginosa and Staphylococcus epidermidis, and were lethal to adherent cells of S. epidermidis. Bromide with 2 carbon spacer groups and 12 carbon alkyl chains (TMEAL-12 Br) effectively reduced microbial adhesion by coating polystyrene and silicone surfaces. The results obtained suggest that, after further studies, gemini QAS might be considered as antimicrobial agents in medicine or industry.

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“…The fusion process of Gemini-based liposomes with model cell membranes has also been followed and elucidated using Differential Scanning Calorimetry (DSC) and uorescence spectroscopy. 25 In many instances Gemini-based formulations were shown to be highly effective for transfection purposes, thus opening the possibility to use these systems in clinical protocols.…”

Section: Introductionmentioning

confidence: 99%

Time resolved SAXS to study the complexation of siRNA with cationic micelles of divalent surfactants

et al. 2013

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The complexation of siRNA (small interfering RNA) with cationic micelles was studied using time dependent synchrotron SAXS. Micelles were formed by two types of divalent cationic surfactants, i.e. Gemini bis(quaternary ammonium) bromide with variable spacer length (12-3-12, 12-6-12, 12-12-12) and a weak electrolyte surfactant (SH14) with triazine head. Immediately after mixing (t < 50 ms), new large aggregates appeared in solution and the scattering intensity at low q increased. Concomitantly, the presence of a quasi-Bragg peak at q ∼ 1.5 nm(-1) indicated core structuring within the complexes. We hypothesize that siRNA and micelles are alternately arranged into "sandwiches", forming domains with internal structural coherence. The process of complex reorganization followed a first-order kinetics and was completed in less than about 5 minutes, after which a steady state was reached. Aggregates containing Geminis were compact globular structures whose gyration radii Rg depended on the spacer length and were in the order of 7-27 nm. Complexes containing SH14 (Rg = 14-16 nm) were less ordered and possessed a looser internal arrangement. The obtained data, joint with previous structural investigation using Dynamic Light Scattering, Zeta Potential and Small Angle Neutron Scattering, are encouraging evidence for using these systems in biological trials. In fact we showed that transfection agents can be obtained by simply mixing a micelle solution of the cationic surfactant and a siRNA solution, both of which are easily prepared and stable.

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Fusion of gemini based cationic liposomes with cell membrane models: implications for their biological activity

Cited by 30 publications

References 34 publications

A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells

A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells

Antibacterial Activity of Alanine‐Derived Gemini Quaternary Ammonium Compounds

Time resolved SAXS to study the complexation of siRNA with cationic micelles of divalent surfactants

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