TY - JOUR
T1 - Quaternization enhances the transgene expression efficacy of aminoglycoside-derived polymers
AU - Miryala, Bhavani
AU - Feng, Yunpeng
AU - Omer, Ala
AU - Potta, Thrimoorthy
AU - Rege, Kaushal
N1 - Funding Information: We are grateful to the NIH/NIGMS (Grant 1R01GM093229-01A1 ) for financial support of this study. The authors also thank Dr. Yanqing Tian and Professor Deirdre Meldrum, Center for Biosignatures Discovery Automation (CBDA), The Biodesign Institute, ASU, for access to the Zetasizer Nanosystems Nano-ZS instrument. The authors also thank Professor Robert Ros and Bryant Doss (graduate student), Department of Physics ASU, for AFM studies, including acquiring and processing AFM images. Publisher Copyright: © 2015 Elsevier B.V. All rights reserved.
PY - 2015/7/15
Y1 - 2015/7/15
N2 - 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 1H 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.
AB - 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 1H 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.
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U2 - 10.1016/j.ijpharm.2015.04.026
DO - 10.1016/j.ijpharm.2015.04.026
M3 - Article
C2 - 25888800
SN - 0378-5173
VL - 489
SP - 18
EP - 29
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -