Urocanic acid improves transfection efficiency of polyphosphazene with primary amino groups for gene delivery.
Urocanic acid improves transfection efficiency of polyphosphazene with primary amino groups for gene delivery.
复制标题
尿刊酸可提高具有伯氨基的聚磷腈用于基因递送的转染效率。
DOI：
10.1021/bc900267g
复制
发表时间：
2010
影响因子：
4.7
通讯作者：
Yaping Li
中科院分区：
文献类型：
--
作者：
Yongxin Yang;Zhiwen Zhang;Lingli Chen;Wangwen Gu;Yaping Li
合成了可生物降解的含伯氨基的阳离子聚（2-（2-氨基乙氧基）乙氧基）磷腈（PAEP）及其衍生物尿刊酸（UA）修饰的PAEP（UA-PAEP），并研究了其基因传递性能。结果表明，当聚合物/DNA比（N/P）为35时，PAEP可将DNA凝聚成粒径约为120 nm的复合纳米粒子，在此条件下PAEP/DNA复合纳米粒子（PACNs）在完全培养基中显示出高效的转染活性。与取代度为7%的UA（UA-PAEP 7）偶联后，UA-PAEP 7/DNA复合物纳米颗粒（UP 7 CNs）的转染效率高于PACNs和UA-PAEP 25/DNA复合物纳米颗粒（UP 25 CNs），细胞毒性低于PEI/DNA复合物纳米颗粒（PEICNs）。使用质子泵抑制剂的转染实验表明，PACNs和UP-PAEP/DNA复合物纳米颗粒（UPCNs）的基因表达依赖于内体酸化过程。乙酸盐溶液（20 mM，pH5.7）提高了UP 7 CN在HeLa和COS 7细胞系中的转染活性，这几乎与N/P比为35的PEICNs相当。因此，UP 7 CNs是一种很有前途的基因传递载体。
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.