- Zhang, Peng-Chi and Wang, Jun and Leong, Kam W. and Mao, Hai-Quan, Ternary complexes comprising polyphosphoramidate gene carriers with different types of charge groups improve transfection efficiency,
Biomacromolecules, vol. 6 no. 1
pp. 54 - 60 [bm040010i] .
(last updated on 2007/04/13)
To understand the influence of charge groups on transfection mediated by polymer complexes, we have synthesized a series of biodegradable and cationic polyphosphoramidates (PPAs) with an identical backbone but different side chains. Our previous study showed that PPA with a spermidine side chain (PPA-SP) showed high transfection efficiency in culture, whereas PPAs with secondary, tertiary, and quaternary amino groups were significantly less efficient. To investigate whether the coexistence of 1° amino charge groups with 3° and 2° amino charge groups in the DNA/polymer complexes would enhance their transfection efficiency, we evaluated a ternary complex system containing DNA and PPAs with 1° amino groups (PPA-SP) and 3° amino groups (PPA-DMA) and a quaternary complex system containing DNA and PPAs with 1° and 2° and 3° amino groups (PPA-EA/PPA-MEA/PPA-DMA), respectively. Ternary complexes mediated 20 and 160 times higher transfection efficiency in COS-7 cells than complexes of DNA with PPA-SP or PPA-DMA alone, respectively. Similarly, quaternary complexes exhibited 8-fold higher transfection efficiency than PPA-EA/DNA complexes. The mechanism of enhancement in transfection efficiency by the mixture carriers appears to be unrelated to the particle size, zeta potential, or DNA uptake. The titration characterization and the transfection experiments using a proton pump inhibitor suggest that the enhancement effect is unlikely due to the slightly improved buffering capacity of the mixture over PPA-SP. This approach represents a simple strategy of developing polymeric gene carriers and understanding the mechanisms of polymer-mediated gene transfer. © 2005 American Chemical Society.
Genes;Synthesis (chemical);Biodegradation;DNA;Amino acids;Titration;