| Zugriffsnummer | 34990 |
| Dokumenttyp | Zeitschriftenartikel |
| Peer Review | unbekannt |
| Sprache | Englisch |
| Titel | Structure–activity relationship study of dendritic polyglycerolamines for efficient siRNA transfection |
| Autor(in); Institution |
Mehrabadi, Fatemeh Sheikhi; Institut für Chemie und Biochemie, Freie Universität Berlin, GERMANY
Hirsch, Ole; 8.3, Biomedizinische Optik, PTB-Berlin
Zeisig, Rainer; Experimental Pharmacology & Oncology GmbH, Berlin, GERMANY
Posocco, Paola; Molecular Simulation Engineering Laboratory, DICAMP, University of Trieste, ITALY
Laurini, Erik; Molecular Simulation Engineering Laboratory, DICAMP, University of Trieste, ITALY
Pricl, Sabrina; Molecular Simulation Engineering Laboratory, DICAMP, University of Trieste, ITALY
Haag, Rainer; Institut für Chemie und Biochemie, Freie Universität Berlin, GERMANY
Kemmner, Wolfgang; Translational Oncology, Experimental and Clinical Research Center, Charité Universitätsmedizin Berlin, GERMANY
Calderón, Marcelo; Institut für Chemie und Biochemie, Freie Universität Berlin, GERMANY
|
| Quelle/Jahr | RSC Advances: 5 (2015), 78760 - 78770 |
| ISSN | 2046-2069 |
| DOI | |
| URL | |
| Verlag | London: RSC Publishing |
| Freie Schlagworte | siRNA transfection ; dendritic polyglycerolamines ; fluorescence imaging ; protoporphyrin-IX |
| Zusammenfassung | Structure–activity relationship studies are pivotal in the development of existing small interfering RNA (siRNA) nanocarriers and in designing new delivery systems. In this paper, we investigated the ability of four dendritic polyglycerolamines (dPG-NH2) with increasing amine degree of functionalization (DF) on dendritic polyglycerol (dPG) to complex DNA by a coupled in silico/in vitro approach. In parallel, we examined our dPG-NH2 analogues for siRNA complexation, cytotoxicity, and transfection efficiency in vitro and in vivo. Our simulation data indicate the most effective nucleic acid affinities for dPG-NH2 analogues with DF ≥ 50%. Concomitantly, the results of in vitro and in vivo transfection studies also demonstrate efficient siRNA transfection only for those dPG-NH2 analogues with DF ≥ 50%. Thus, both MD simulation and siRNA knockdown studies show that a minimum DF per dPG unit (namely 50% on a 10 kDa dPG) is needed to achieve efficient siRNA interaction and successful transfection. |
Zitierung
Mehrabadi, F. S., Hirsch, O., Zeisig, R., Posocco, P., Laurini, E., Pricl, S., Haag, R., Kemmner, W., & Calderón, M. (2015). Structure–activity relationship study of dendritic polyglycerolamines for efficient siRNA transfection. RSC Advances, 5, 78760–78770. https://doi.org/10.1039/c5ra10944b