Branched and linear poly(ethylene imine)-based conjugates: synthetic modification, characterization, and application

Poly(ethylene imine)s (PEIs) are widely used in different applications, but most extensively investigated as non-viral vector systems. The high ability of cationic PEIs to complex and condense negatively charged DNA and RNA combined with their inherent proton sponge behavior accounts for the excelle...

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Published inChemical Society reviews Vol. 41; no. 13; pp. 4755 - 4767
Main Authors Jäger, Michael, Schubert, Stephanie, Ochrimenko, Sofia, Fischer, Dagmar, Schubert, Ulrich S
Format Journal Article
LanguageEnglish
Published England 01.01.2012
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Summary:Poly(ethylene imine)s (PEIs) are widely used in different applications, but most extensively investigated as non-viral vector systems. The high ability of cationic PEIs to complex and condense negatively charged DNA and RNA combined with their inherent proton sponge behavior accounts for the excellent efficiency in gene delivery. Further chemical modifications of the polymer expand the application potential, primarily aiming at increased transfection efficiency, cell selectivity and reduced cytotoxicity. Improvements in the synthesis of tailor-made PEIs in combination with new in-depth analytical techniques offer the possibility to produce highly purified polymers with defined structures. The contemporary strategies towards linear and branched poly(ethylene imine)s with modified surface characteristics, PEI-based copolymers as well as conjugates with bioactive molecules will be discussed. In this regard, the versatile branched PEIs have been successfully modified in a statistical manner, whereas the linear counterparts open avenues to design and synthesize well-defined architectures, in order to exploit their high potential in gene delivery. This review covers synthetic aspects of poly(ethylene imine)s to design well-defined architectures with increased transfection efficiency, cell selectivity and reduced cytotoxicity.
Bibliography:Ulrich S. Schubert was born in Tübingen (Germany) in 1969. He studied chemistry in Frankfurt and Bayreuth (both Germany) and the Virginia Commonwealth University, Richmond (USA). His PhD studies were performed at the Universities of Bayreuth and South Florida/Tampa (USA). After postdoctoral training with J.-M. Lehn at the University in Strasbourg (France), he moved to the TU München (Germany) and obtained his Habilitation in 1999. From 1999-2000 he was Professor at the Center for NanoScience, University of Munich (Germany), and from 2000-2007 Full-Professor at TU Eindhoven (The Netherlands). Currently he holds a chair at the Friedrich-Schiller-University Jena with research interest in nanoparticle systems as sensor and drug delivery devices, supramolecular chemistry, inkjet printing of polymers, polymers for energy, and self-healing materials.
Dagmar Fischer was born in Coburg (Germany) in 1967. She studied pharmacy at the University of Würzburg and received her PhD at the University of Marburg in 1997. After a scientific visit at the Texas Tech University Health Sciences Center in 2002 and 2003, she obtained her Habilitation at the University of Marburg in 2004. From 2004-2008, she was employed as Head of Preclinical Research and Development at Antisense Pharma GmbH. Since 2008, she is Professor for Pharmaceutical Technology at the Friedrich-Schiller-University Jena. Her research is focused on the field of polymeric gene delivery and bacterial nanocellulose as drug delivery systems, all combined with intense toxicological investigations.
Michael Jäger was born in 1979 in Jena (Germany). He studied chemistry at the Friedrich-Schiller-University of Jena (Germany) and McGill University (Canada). For his PhD studies, he moved to Uppsala University (Sweden) to gain further insight into fundamental photosynthetic principles. After a short research stay with J.-P. Sauvage in Strasbourg (France), he finished his PhD thesis in 2009. His research interest covers photoactive compounds and the controlled modular assembly of functional molecules in (polymeric) architectures. Currently, he is working at the Department of Organic and Macromolecular Chemistry at the University in Jena on projects to utilize end-functionalized poly(ethylene imine)s.
Sofia Ochrimenko was born in 1983 in Jena (Germany). She studied pharmacy at the Friedrich-Schiller-University Jena (Germany) from 2001 to 2005. She passed her practical year in a pharmacy in Ilmenau and in the Spitalpharmacy of the University Hospital Basel (Switzerland). From 2007-2009 she worked as a pharmacist at the hospital pharmacy of the SRH Wald-Klinikum Gera (Germany). In 2010, she joined the research groups of Dagmar Fischer and Ulrich S. Schubert as a PhD student at the Friedrich-Schiller-University Jena (Germany) in the NanoConSens project.
Stephanie Schubert (née Hornig) was born in 1981 in Zwickau (Germany). She obtained her MS in chemistry at the Friedrich-Schiller-University of Jena (Germany) in 2005. After research activities at Virginia Tech (Blacksburg, USA), she finished her PhD studies in 2008 in the field of polysaccharide chemistry at the University in Jena in the group of T. Heinze. During a postdoctoral training with J. M. J. Frechét at UC Berkeley (USA), she gained further experiences in polymers as gene delivery devices. She is currently working on projects related to nanoparticles for drug delivery and sensor applications at the Pharmaceutical Department at the University in Jena.
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ISSN:0306-0012
1460-4744
DOI:10.1039/c2cs35146c