Secure and effective gene vector of polyamidoamine dendrimer pharraac eutically modified with anionic polymer
Secure and effective gene vector of polyamidoamine dendrimer pharraac eutically modified with anionic polymer
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阴离子聚合物共修饰聚酰胺胺树枝状聚合物法拉克的安全有效的基因载体
DOI：
10.1002/jps.22701
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Sasaki H
中科院分区：
文献类型：
--
作者：
Kurosaki T;Yamashita Y;Aki K;Harasawa H;Nakagawa H;Kodama Y;Higuchi N;Nakamura T;Kitahara T;Sasaki H
本研究的目的是开发一种新型的基因载体，聚酰胺胺（PAMAM）树枝状复合物药物修饰，基于静电相互作用，由各种阴离子聚合物。γ-聚谷氨酸（γ-PGA）/PAMAM树枝状复合物和α-PGA/PAMAM树枝状复合物形成稳定的复合物，尽管α-聚天冬氨酸和肝素从复合物中释放pDNA。阴离子聚合物的加入降低了复合物的电位，尽管它对复合物的尺寸没有很大影响。作为小鼠黑色素瘤细胞的体外基因表达研究的结果，我们发现γ-PGA/PAMAM树枝状复合物显示出与PAMAM树枝状复合物相当的高基因表达，尽管α-PGA/PAMAM树枝状复合物显示出较低的基因表达。将γ-PGA/PAMAM树枝状复合物尾静脉注射到小鼠中也导致脾和肺中的高基因表达。γ-PGA/PAMAM树枝状复合物显示无细胞毒性和无凝集，尽管在PAMAM树枝状复合物中观察到严重的细胞毒性和凝集。因此，我们发现pDNA、PAMAM树枝状聚合物和γ-PGA的复合物在体外和体内显示出更高的基因表达，并且毒性显著降低。该复合物具有一定的应用价值，有望成为一种安全有效的基因载体。© 2011 Wiley利斯公司和American Pharmacologist Association J Pharm Sci 100：4855-4863，2011
The purpose of this study was to develop a new type of gene vector, polyamidoamine (PAMAM) dendriplex pharmaceutically modified, based on electrostatic interactions, by various anionic polymers. The γ‐polyglutamic acid (γ‐PGA)/PAMAM dendriplex and the α‐PGA/PAMAM dendriplex formed a stable complex, although α‐polyaspartic acid and heparin released pDNA from the complex. The addition of anionic polymer decreased the ζ‐potential, although it did not greatly affect the size of the complex. As a result of anin vitrogene expression study of mouse melanoma cells, we found that the γ‐PGA/PAMAM dendriplex showed high gene expression comparable to the PAMAM dendriplex, although the α‐PGA/PAMAM dendriplex showed lower gene expression. Tail vein injection of the γ‐PGA/PAMAM dendriplex into mice also led to high gene expression in the spleen and lung. The γ‐PGA/PAMAM dendriplex showed no cytotoxicity and no agglutination, although severe cytotoxicity and agglutination were observed in the PAMAM dendriplex. Thus, we discovered that complexes of pDNA, PAMAM dendrimers, and γ‐PGA showed higher gene expressionin vitroandin vivo, and markedly lower toxicity. This complex is valuable and is expected to be a safe and effective gene vector. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4855–4863, 2011