Urocanic Acid Improves Transfection Efficiency of Polyphosphazene with Primary Amino Groups for Gene Delivery

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• 作者：Yongxin Yang ; Zhiwen Zhang ; Lingli Chen ; Wangwen Gu ; Yaping Li
• 刊名：Bioconjugate Chemistry
• 出版年：2010
• 出版时间：March 17, 2010
• 年：2010
• 卷：21
• 期：3
• 页码：419-426
• 全文大小：293K
• 年卷期：v.21,no.3(March 17, 2010)
• ISSN：1520-4812

文摘

The biodegradable cationic poly(2-(2-aminoethoxy)ethoxy)phosphazene (PAEP) bearing primary amino groups and a new PAEP derivative, urocanic acid (UA) modified PAEP (UA-PAEP), were synthesized and investigated for gene delivery. The results indicated that PAEP was able to condense DNA into complex nanoparticles with the size around 120 nm at the polymer/DNA ratio (N/P) of 35, at which PAEP/DNA complex nanoparticles (PACNs) showed efficient transfection activity in complete medium. After conjugating with UA at the substitution degree of 7% (UA-PAEP7), UA-PAEP7/DNA complex nanoparticles (UP7CNs) exhibited higher transfection efficiency than PACNs and UA-PAEP25/DNA complex nanoparticles (UP25CNs) and much lower cytotoxicity compared with PEI/DNA complex nanoparticles (PEICNs). The transfection experiment using a proton pump inhibitor suggested that the gene expression of PACNs and UP-PAEP/DNA complex nanoparticles (UPCNs) was dependent on the endosomal acidification process. The acetate solution (20 mM, pH5.7) improved the transfection activity of UP7CNs in HeLa and COS 7 cell lines, which was almost comparable to PEICNs at the N/P ratio of 35. Therefore, the results suggested that UP7CNs could be a promising carrier for gene delivery.