Physicochemical and biological study of selected hydrophobic polyethylenimine-based polycationic liposomes and their complexes with DNA

Andrea Masotti, Fabiola Moretti, Francesca Mancini, Giuseppina Russo, Nicoletta Di Lauro, Paola Checchia, Carlotta Marianecci, Maria Carafa, Eleonora Santucci, Giancarlo Ortaggi

Research output: Contribution to journalArticlepeer-review

Abstract

Non-viral gene therapy is based on the development of efficient and safe gene carrier systems able to transfer DNA into cells. Polyethylenimine (PEI), the most promising non-viral vector, with its high cationic-charge-density potential is able (1) to compact DNA in complexes (polyplexes) smaller than those formed by liposomes (lipoplexes) and (2) to destabilize the endosomal membrane by a 'proton sponge' effect. Several PEI's hydrophobic modifications were reported in the last several years but in some cases a reduced transfection efficiency was observed. The mechanism underlying this phenomenon is not well understood so far. In order to extensively investigate these mechanisms, we reported a physicochemical and biological study of selected hydrophobic PEI's derivatives grafted with chains of different length and percentages of substitution able to form vesicles (polycationic liposomes) and to bind DNA. Their properties were studied by means of dynamic light scattering, freeze-fracture microscopy, potentiometric titrations, gel retardation assays, polyanion exchange reactions, toxicity assays, in vitro transfections, and fluorescence microscopy. Our results indicate that even if polyplexes are able to pass through the cellular membrane, the stability of PEI's hydrophobic polyplexes likely explain their different transfection efficiency in vitro.

Original languageEnglish
Pages (from-to)1504-1515
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume15
Issue number3
DOIs
Publication statusPublished - Feb 1 2007

Keywords

  • DNA complexes
  • Polycationic vectors
  • Polyethylenimine
  • Transfection
  • Translocation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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