Addition of free poloxamer 407 to a new gene vector P407-PEI-K12 solution forms a sustained-release in situ hypergel that enhances cell transfection and extends gene expression
Addition of free poloxamer 407 to a new gene vector P407-PEI-K12 solution forms a sustained-release in situ hypergel that enhances cell transfection and extends gene expression
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将游离泊洛沙姆 407 添加到新基因载体 P407-PEI-K12 溶液中，形成缓释原位超凝胶，增强细胞转染并延长基因表达
DOI：
10.3892/ol.2019.9944
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发表时间：
2019-01
期刊：
影响因子：
2.9
通讯作者：
Wang Jun
中科院分区：
文献类型：
--
作者：
Shu Hongmei;Zhang Yaguang;Zhang Min;Wu Junwen;Cui Mingxiao;Liu Kehai;Wang Jun
为了解决人们对聚乙烯亚胺(PEI)效率/细胞毒性比和肿瘤靶向效应的担忧，将低分子聚乙烯亚胺(PEI)与P407进行交联，并进一步偶联由肿瘤靶向多肽tLyP-1和核定位序列组成的双功能肽K12，合成了用于传递癌症治疗基因的非病毒基因载体泊洛沙姆407(P407)-PEI-K12。此外，在聚合物/DNA复合体溶液中加入游离P407形成了温度敏感的原位凝胶-P407/P407-PEI-K12/DNA复合体，从而提高了基因缓释传递的效果和转染率。体外研究P407-PEI-K12对Hela细胞的特异性、细胞毒性和基因转染率。该聚合物有效地阻止了DNase I对质粒DNA的降解，并具有明显的血清耐受能力。琼脂糖凝胶电泳法显示，质粒DNA得到了有效的浓缩和保护。P407-PEI-K12h(P407-PEI与K12的摩尔比为1：10)的转染率较高，当聚合物与质粒DNA的质量比为20：1时，游离P407对聚合物/DNA复合体的转染率高达0.09%。P407/P407-PEI-K12-h/DNA凝胶复合体的半衰期为228min，在不同释放时间，P407/P407-PEI-K12-h/DNA复合体的转染率明显高于P407-PEI-K12-h/DNA复合体。
To address the concern around the efficiency/cytotoxicity ratio and the tumor-targeting effects of polyethylenimine (PEI), is a non-viral gene vector used for the delivery of the cancer therapy gene, poloxamer 407 (P407)-PEI-K12, was synthesized by cross-linking low-molecular weight PEI with P407 and further coupling a bifunctional peptide, K12, which is comprised of the tumor-targeting peptide tLyP-1 and the nuclear localization sequence. Furthermore, the addition of free P407 into the polymer/DNA complex solution produced a temperature-sensitive in situ gel-P407/P407-PEI-K12/DNA complex, which improved the effects of sustained-release gene delivery and transfection efficiency. The specificity, cytotoxicity and gene transfection efficiency of P407-PEI-K12 was investigated in Hela cells in vitro. The polymer efficiently prevented the degradation of plasmid DNA by DNase I and had a marked ability for serum tolerance. Agarose gel electrophoresis revealed that plasmid DNA was efficiently condensed and protected. The higher transfection efficiency of P407-PEI-K12h (the molar ratio of P407-PEI and K12 is 1:10) was achieved with a polymer and plasmid DNA ratio (w/w) of 20:1. The ability of free P407 to promote the transfection of the polymer/DNA complex was high (0.09%). The half-life of the P407/P407-PEI-K12-h/DNA gel complex was 228 min, and the transfection efficiency of the P407/P407-PEI-K12-h/DNA complex was markedly higher compared to that of the P407-PEI-K12-h/DNA complex at various release times.
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影响因子：
14
作者：
J. Shen;D. Zhao;W. Li;Q. Hu;Q. Wang;F. Xu;G. Tang
通讯作者：
J. Shen;D. Zhao;W. Li;Q. Hu;Q. Wang;F. Xu;G. Tang
DOI：
10.1016/j.ejpb.2017.01.008
发表时间：
2017-05-01
影响因子：
4.9
作者：
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通讯作者：
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影响因子：
10.8
作者：
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通讯作者：
Siepmann, J.
影响因子：
11.2
作者：
Ambattu, Lizebona August;Rekha, M. R.
通讯作者：
Rekha, M. R.
DOI：
10.1016/j.ejpb.2014.08.008
发表时间：
2014-11-01
影响因子：
4.9
作者：
Cespi, Marco;Bonacucina, Giulia;Mosconi, Gilberto
通讯作者：
Mosconi, Gilberto