title: Parallel high-throughput screening of polymer vectors for nonviral gene delivery: evaluation of structure-property relationships of transfection.
abstract: In recent years, "high-throughput" (HT) has turned into a keyword in polymer research. In this study, we present a novel HT workflow for the investigation of cationic polymers for gene delivery applications. For this purpose, various poly(ethylene imine)s (PEI) were used as representative vectors and investigated via HT-assays in a 96-well plate format, starting from polyplex preparation up to the examination of the transfection process. In detail, automated polyplex preparation, complex size determination, DNA binding affinity, polyplex stability, cytotoxicity, and transfection efficiency were performed in the well plate format. With standard techniques, investigation of the biological properties of polymers is quite time-consuming, so only a limited number of materials and conditions (such as pH, buffer composition, and concentration) can be examined. The approach described here allows many different polymers and parameters to be tested for transfection properties and cytotoxicity, giving faster insights into structure-activity relationships for biological activity.
authors.affiliation: Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena , Humboldtstraße 10, 07743 Jena, Germany.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Rinkenauer
authors.forename: Antje
authors.initials: A
authors.lastname: Vollrath
authors.forename: Anja
authors.initials: A
authors.lastname: Schallon
authors.forename: Lutz
authors.initials: L
authors.lastname: Tauhardt
authors.forename: Kristian
authors.initials: K
authors.lastname: Kempe
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schubert
authors.forename: Dagmar
authors.initials: D
authors.lastname: Fischer
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Schubert
mesh_terms: D002412:Cations / Q000138:chemical synthesis / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D018014:Gene Transfer Techniques / Q000295:instrumentation; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D057809:HEK293 Cells; D057166:High-Throughput Screening Assays / Q000295:instrumentation; D006801:Humans; D007097:Imines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010316:Particle Size; D011095:Polyethylenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D002412:Cations; D007097:Imines; D011095:Polyethylenes; C505405:poly(ethylene imine)