Nuclear localization of cationic solid lipid nanoparticles containing Protamine as transfection promoter

Eleonora Vighi, Monica Montanari, Barbara Ruozi, Giovanni Tosi, Alessandro Magli, Eliana Leo

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Protamine has attracted much attention as DNA condenser and nuclear transfer enhancer although the excess of hydrophilicity and the strong DNA pack restrain its potentialities. In order to overcome this limitation, we added Protamine in the composition of solid lipid nanoparticles (SLN-Protamine) and we compared this carrier with the same kind of SLN containing Esterquat 1 instead of Protamine (SLN-EQ1). Carriers cytotoxicity was assessed on COS-I cells evaluating the cell cycle by propidium iodide test, while the transfection efficiency was studied using pEGFP as plasmid model. The cell penetrating activity of Protamine inside the lipid vectors was evaluated studying cell internalization by confocal microscopy using Red Nile-labeled carriers. SLN-Protamine:pDNA showed a mean diameter five-times smaller than the size of SLN-EQ1:pDNA and a remarkably lesser cytotoxicity. Transfection by SLN-Protamine:pDNA was seven-times more effective compared with the Protamine:pDNA polyplexes while no transfection capacity was observed for SLN-EQ1:pDNA complexes due to their inability to be internalized owing to their larger dimension. Red Nile-SLN-Protamine were localized in endocytic-like vesicles into the nuclear membrane suggesting the inclusion of Protamine in nano-lipophilic systems may enhance the reduction in the complex dimensions, the nuclear pDNA translocation and the pDNA release in the cells.

Original languageEnglish (US)
Pages (from-to)384-393
Number of pages10
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume76
Issue number3
DOIs
StatePublished - Nov 2010

Bibliographical note

Funding Information:
This work was financially supported by the Fondazione Cassa di Risparmio di Modena. Thanks are due to Dr. A. Tombesi for the technical advice in the confocal analysis and to Dr. I. Silvetti for the editing of English grammar.

Keywords

  • Confocal microscopy
  • Gene delivery
  • Propidium iodide
  • Protamine
  • Solid lipid nanoparticles

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