Title of article :
Physicochemical and biological study of selected hydrophobic polyethylenimine-based polycationic liposomes and their complexes with DNA Original Research Article
Author/Authors :
Andrea Masotti، نويسنده , , Fabiola Moretti، نويسنده , , Francesca Mancini، نويسنده , , Giuseppina Russo، نويسنده , , Nicoletta Di Lauro، نويسنده , , Paola Checchia، نويسنده , , Carlotta Marianecci، نويسنده , , Maria Carafa، نويسنده , , Eleonora Santucci، نويسنده , , Giancarlo Ortaggi، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2007
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.
Keywords :
Polycationic vectors , DNA complexes , Transfection , Polyethylenimine , Translocation
Journal title :
Bioorganic and Medicinal Chemistry
Journal title :
Bioorganic and Medicinal Chemistry