Nonviral Gene-Delivery by Highly Fluorinated Gemini Bispyridinium Surfactant-Based DNA Nanoparticles

J Colloid Interface Sci. 2017 Feb 1;487:182-191. doi: 10.1016/j.jcis.2016.10.032. Epub 2016 Oct 15.

Abstract

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 298K, 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.

Keywords: Atomic force microscopy; DNA nanoparticles; DNA-fluorinated surfactant interaction; Gemini surfactants; Gene delivery; Heterocyclic gemini cationic surfactants; Phase transition in solution; Synthetic vectors for gene delivery.

MeSH terms

  • Cell Line, Tumor
  • DNA / chemistry*
  • DNA / genetics
  • DNA / metabolism
  • Electrophoretic Mobility Shift Assay
  • Halogenation
  • Humans
  • Microscopy, Atomic Force
  • Muscle Cells / cytology
  • Muscle Cells / metabolism
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Phosphatidylethanolamines / chemistry*
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Quaternary Ammonium Compounds / chemistry*
  • Structure-Activity Relationship
  • Thermodynamics
  • Transfection / methods*

Substances

  • Phosphatidylethanolamines
  • Quaternary Ammonium Compounds
  • dioleoyl phosphatidylethanolamine
  • DNA