Synthesis and Characterization of New Permanently Charged Poly(amidoammonium) Salts and Evaluation of Their DNA Complexes for Gene Transport

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• 作者：Pascal Y. Vuillaume ; M&eacute ; lanie Brunelle ; Marie-Rose Van Calsteren ; Sylvette Laurent-Lewandowski ; Andr&eacute ; B&eacute ; gin ; Raymond Lewandowski ; Brian G. Talbot ; and Youssef ElAzhary
• 刊名：Biomacromolecules
• 出版年：2005
• 出版时间：May 2005
• 年：2005
• 卷：6
• 期：3
• 页码：1769 - 1781
• 全文大小：524K
• 年卷期：v.6,no.3(May 2005)
• ISSN：1526-4602

文摘

A new series of linear and permanently charged poly(amidoammonium) salts were synthesized in order toinvestigate the influence of their ionic and hydrophobic contents on both the cytotoxicity and the transfectionmediated by polycation-DNA complexes. The poly(amidoammonium) salts were prepared by chemicalmodification of a parent poly(amidoamine) containing two tertiary amino groups per structural unit: oneincorporated into the main chain and the other fixed at the end of a short bismethylene spacer. The permanentcharges were introduced through a quaternization reaction involving iodomethane or 1-iodododecane as analkylating agent. Under appropriate conditions, the methylation reaction was found to be regioselective,allowing the quaternization of either the side chains or both the side chains and the backbone. Underphysiological salt conditions (150 mM NaCl), all of the poly(amidoammonium) salts self-assembled withDNA to form complexes. High proportions of highly quaternized polycation provided better definedmorphology to the polycation-DNA complexes. Complexes formed from unquaternized polycation wereless cytotoxic than branched poly(ethyleneimine) (25 kDa). At high polycation-DNA weight ratios, theintroduction of permanent charges generated a significant increase in the cytotoxicity, but no patent correlationcould be established with the amount and the position of the permanent charges. Only complexes formedfrom polycations with quaternized backbone were able to generate significant gene expression, which wasputatively attributed to a better defined toroidal-like morphology together with a higher stability, as suggestedby zeta potential measurements. The incorporation of dodecane side chains on highly charged polycationsseverely amplified the cytotoxicity so that, in return, the transfection level was dramatically affected.