Nonviral gene-delivery by highly fluorinated gemini bispyridinium surfactant-based DNA nanoparticles

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• 作者：Emilia Fisicaro^a ; ^{emilia.fisicaro@unipr.it" class="auth_mail" title="E-mail the corresponding author} ; Carlotta Compari^a ; Franco Bacciottini^a ; Laura Contardi^a ; Erika Pongiluppi^a ; Nadia Barbero^b ; Guido Viscardi^b ; Pierluigi Quagliotto^b ; Gaetano Donofrio^c ; Marie Pierre Krafft^d
• 关键词：DNA nanoparticles ; Gene delivery ; Gemini surfactants ; Heterocyclic gemini cationic surfactants ; Synthetic vectors for gene delivery ; Atomic force microscopy ; Phase transition in solution ; DNA-fluorinated surfactant interaction
• 刊名：Journal of Colloid and Interface Science
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：487
• 期：Complete
• 页码：182-191
• 全文大小：2514 K

文摘

Biological and thermodynamic properties of a new homologous series of highly fluorinated bispyridinium cationic gemini surfactants, differing in the length of the spacer bridging the pyridinium polar heads in 1,1′ position, are reported for the first time. Interestingly, gene delivery ability is closely associated with the spacer length due to a structural change of the molecule in solution. This conformation change is allowed when the spacer reaches the right length, and it is suggested by the trends of the apparent and partial molar enthalpies vs molality. To assess the compounds’ biological activity, they were tested with an agarose gel electrophoresis mobility shift assay (EMSA), MTT proliferation assay and Transient Transfection assays on a human rhabdomyosarcoma cell line. Data from atomic force microscopy (AFM) allow for morphological characterization of DNA nanoparticles. Dilution enthalpies, measured at 298 K, enabled the determination of apparent and partial molar enthalpies vs molality. All tested compounds (except that with the longest spacer), at different levels, can deliver the plasmid when co-formulated with 1,2-dioleyl-sn-glycero-3-phosphoethanolamine (DOPE). The compound with a spacer formed by eight carbon atoms gives rise to a gene delivery ability that is comparable to that of the commercial reagent. The compound with the longest spacer compacts DNA in loosely condensed structures by forming bows, which are not suitable for transfection. Regarding the compounds’ hydrogenated counterparts, the tight relationship between the solution thermodynamics data and their biological performance is amazing, making “old” methods the foundation to deeply understanding “new” applications.