title: Quaternization enhances the transgene expression efficacy of aminoglycoside-derived polymers.
abstract: The objective of the present study was to synthesize and investigate the transgene expression efficacy of quaternized derivatives of aminoglycoside polymers in different cancer cell lines. A series of glycidyltrimethylammonium chloride (GTMAC) derivatives of aminoglycoside polymers (GTMAC-AM polymers), containing varying degrees of quaternization (13-45%), were synthesized. The structures and properties of GTMAC-AM polymers were investigated using FT-IR and (1)H NMR spectroscopy. Physicochemical factors that influence transgene expression efficacy including DNA binding, hydrodynamic size, zeta potential and cytotoxicity, were determined. Formation of polymer-plasmid DNA complexes was also visualized using atomic force microscopy. GTMAC-AM polymers demonstrated higher transgene expression efficacies compared to their parent polymers, 25 kDa poly(ethyleneimine), as well as Lipofectamine-3000. Our results indicate that quaternization enhances the transgene expression efficacy and reduces the cytotoxicity of aminoglycoside-derived polymers, making it an attractive strategy for nucleic acid delivery with these new materials.
authors.affiliation: Chemical Engineering, School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ 85287-6106, USA.
authors.forename: Bhavani
authors.initials: B
authors.lastname: Miryala
authors.affiliation: Biomedical Engineering, School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287-6106, USA.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Chemical Engineering, School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ 85287-6106, USA.
authors.forename: Ala
authors.initials: A
authors.lastname: Omer
authors.affiliation: Chemical Engineering, School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ 85287-6106, USA.
authors.forename: Thrimoorthy
authors.initials: T
authors.lastname: Potta
authors.affiliation: Chemical Engineering, School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ 85287-6106, USA. Electronic address: kaushal.rege@asu.edu.
authors.forename: Kaushal
authors.initials: K
authors.lastname: Rege
mesh_terms: D000617:Aminoglycosides / Q000008:administration & dosage / Q000737:chemistry*; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry*; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000737:chemistry*; D015870:Gene Expression; D006801:Humans; D049409:Luciferases, Firefly / Q000235:genetics*; D010957:Plasmids; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000737:chemistry*; D019076:Transgenes / Q000235:genetics*
chemical_list: D000617:Aminoglycosides; D004852:Epoxy Compounds; D011108:Polymers; D000644:Quaternary Ammonium Compounds; C045006:glycidyl trimethylammonium; D004247:DNA; D049409:Luciferases, Firefly