Publikationsdatenbank

Glycine-terminated dendritic amphiphiles for nonviral gene delivery (2012)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Malhotra, Shashwat

Bauer, Hannah

Tschiche, Ariane

Staedtler, Anna Maria

Mohr, Andreas

Calderón, Marcelo

Parmar, Virinder S

Hoeke, Lena

Sharbati, Soroush

Einspanier, Ralf

Haag, Rainer

Forschungsprojekt

Biokompatible siRNA-Nanotransporter für das zielgerichtete mRNAknock-down in vivo - Teilvorhaben: Synthese, Charakterisierung und biologische Evaluierung dendritischer Polyamine, bzw. Amphiphile 1., 2. u. 3. Generation

Quelle

Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences / publ. by the American Chemical Society

Bandzählung: 13

Heftzählung: 10

Seiten: 3087 – 3098

ISSN: 1525-7797

Sprache

Englisch

Verweise

DOI: 10.1021/bm300892v

Pubmed: 22877231

Kontakt

Institut für Veterinär-Biochemie

Oertzenweg 19 b
14163 Berlin
+49 30 838 62225
biochemie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Development of nonviral vectors for the successful application of gene therapy through siRNA/DNA transfection of cells is still a great challenge in current research. (1, 2) In the present study, we have developed multivalent polyglycerol dendron based amphiphiles with well-defined molecular structures that express controlled glycine arrays on their surfaces. The structure-activity relationships with respect to the siRNA complexation, toxicity, and transfection profiles were studied with synthesized amphiphilic polycations. Our findings revealed that a second-generation amphiphilic dendrimer (G2-octaamine, 4) that has eight amine groups on its surface and a hydrophobic C-18 alkyl chain at the core of the dendron, acts as an efficient vector to deliver siRNA and achieve potent gene silencing by investigating the knockdown of luciferase and GAPDH gene activity in HeLa cells. Interestingly, the amphiphilic vector is nontoxic even at higher ratio of N/P 100. To the best of our knowledge this is the first example of successful in vitro siRNA transfection using dendritic amphiphiles. We believe that this supramolecular complex may serve as a new promising alternative for nonviral siRNA delivery systems and will be investigated for in vivo siRNA delivery in the future.