Cargando…

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

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 biologic...

Descripción completa

Detalles Bibliográficos
Autores principales: Massa, Michele, Rivara, Mirko, Pertinhez, Thelma A., Compari, Carlotta, Donofrio, Gaetano, Cristofolini, Luigi, Orsi, Davide, Franceschi, Valentina, Fisicaro, Emilia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145364/
https://www.ncbi.nlm.nih.gov/pubmed/37110819
http://dx.doi.org/10.3390/molecules28083585
_version_ 1785034315951767552
author Massa, Michele
Rivara, Mirko
Pertinhez, Thelma A.
Compari, Carlotta
Donofrio, Gaetano
Cristofolini, Luigi
Orsi, Davide
Franceschi, Valentina
Fisicaro, Emilia
author_facet Massa, Michele
Rivara, Mirko
Pertinhez, Thelma A.
Compari, Carlotta
Donofrio, Gaetano
Cristofolini, Luigi
Orsi, Davide
Franceschi, Valentina
Fisicaro, Emilia
author_sort Massa, Michele
collection PubMed
description 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 ψ-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.
format Online
Article
Text
id pubmed-10145364
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-101453642023-04-29 Chemico-Physical Properties of Some 1,1′-Bis-alkyl-2,2′-hexane-1,6-diyl-bispyridinium Chlorides Hydrogenated and Partially Fluorinated for Gene Delivery Massa, Michele Rivara, Mirko Pertinhez, Thelma A. Compari, Carlotta Donofrio, Gaetano Cristofolini, Luigi Orsi, Davide Franceschi, Valentina Fisicaro, Emilia Molecules Article 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 ψ-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. MDPI 2023-04-20 /pmc/articles/PMC10145364/ /pubmed/37110819 http://dx.doi.org/10.3390/molecules28083585 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Massa, Michele
Rivara, Mirko
Pertinhez, Thelma A.
Compari, Carlotta
Donofrio, Gaetano
Cristofolini, Luigi
Orsi, Davide
Franceschi, Valentina
Fisicaro, Emilia
Chemico-Physical Properties of Some 1,1′-Bis-alkyl-2,2′-hexane-1,6-diyl-bispyridinium Chlorides Hydrogenated and Partially Fluorinated for Gene Delivery
title Chemico-Physical Properties of Some 1,1′-Bis-alkyl-2,2′-hexane-1,6-diyl-bispyridinium Chlorides Hydrogenated and Partially Fluorinated for Gene Delivery
title_full Chemico-Physical Properties of Some 1,1′-Bis-alkyl-2,2′-hexane-1,6-diyl-bispyridinium Chlorides Hydrogenated and Partially Fluorinated for Gene Delivery
title_fullStr Chemico-Physical Properties of Some 1,1′-Bis-alkyl-2,2′-hexane-1,6-diyl-bispyridinium Chlorides Hydrogenated and Partially Fluorinated for Gene Delivery
title_full_unstemmed Chemico-Physical Properties of Some 1,1′-Bis-alkyl-2,2′-hexane-1,6-diyl-bispyridinium Chlorides Hydrogenated and Partially Fluorinated for Gene Delivery
title_short Chemico-Physical Properties of Some 1,1′-Bis-alkyl-2,2′-hexane-1,6-diyl-bispyridinium Chlorides Hydrogenated and Partially Fluorinated for Gene Delivery
title_sort chemico-physical properties of some 1,1′-bis-alkyl-2,2′-hexane-1,6-diyl-bispyridinium chlorides hydrogenated and partially fluorinated for gene delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145364/
https://www.ncbi.nlm.nih.gov/pubmed/37110819
http://dx.doi.org/10.3390/molecules28083585
work_keys_str_mv AT massamichele chemicophysicalpropertiesofsome11bisalkyl22hexane16diylbispyridiniumchlorideshydrogenatedandpartiallyfluorinatedforgenedelivery
AT rivaramirko chemicophysicalpropertiesofsome11bisalkyl22hexane16diylbispyridiniumchlorideshydrogenatedandpartiallyfluorinatedforgenedelivery
AT pertinhezthelmaa chemicophysicalpropertiesofsome11bisalkyl22hexane16diylbispyridiniumchlorideshydrogenatedandpartiallyfluorinatedforgenedelivery
AT comparicarlotta chemicophysicalpropertiesofsome11bisalkyl22hexane16diylbispyridiniumchlorideshydrogenatedandpartiallyfluorinatedforgenedelivery
AT donofriogaetano chemicophysicalpropertiesofsome11bisalkyl22hexane16diylbispyridiniumchlorideshydrogenatedandpartiallyfluorinatedforgenedelivery
AT cristofoliniluigi chemicophysicalpropertiesofsome11bisalkyl22hexane16diylbispyridiniumchlorideshydrogenatedandpartiallyfluorinatedforgenedelivery
AT orsidavide chemicophysicalpropertiesofsome11bisalkyl22hexane16diylbispyridiniumchlorideshydrogenatedandpartiallyfluorinatedforgenedelivery
AT franceschivalentina chemicophysicalpropertiesofsome11bisalkyl22hexane16diylbispyridiniumchlorideshydrogenatedandpartiallyfluorinatedforgenedelivery
AT fisicaroemilia chemicophysicalpropertiesofsome11bisalkyl22hexane16diylbispyridiniumchlorideshydrogenatedandpartiallyfluorinatedforgenedelivery