Biscarbamate cross-linked low molecular weight Polyethylenimine polycation as an efficient intra-cellular delivery cargo for cancer therapy.
Biscarbamate cross-linked low molecular weight Polyethylenimine polycation as an efficient intra-cellular delivery cargo for cancer therapy.
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双氨基甲酸酯交联低分子量聚乙烯亚胺聚阳离子作为癌症治疗的有效细胞内递送货物
DOI：
10.1186/1477-3155-12-13
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发表时间：
2014-04-06
影响因子：
10.2
通讯作者：
Yuan W
中科院分区：
文献类型：
--
作者：
Ge X;Feng J;Chen S;Zhang C;Ouyang Y;Liu Z;Yuan W
基因治疗的一个挑战是将 DNA/siRNA 有效递送至患病细胞。 siRNA 的物理化学特性（例如高分子量、负电荷和亲水性）阻止了大多数细胞跨质膜的被动扩散。治疗上可行的用于细胞内递送基因材料的载体应完成一系列任务，例如：浓缩核酸、保护核酸在体内不渗漏、促进内体逃逸以及将DNA/siRNA释放到靶位点。为了满足这些要求，开发了一种基于聚阳离子合成的高效基因载体，用于体外和体内 siRNA 递送。该聚合物由1, 4-丁二醇双（氯甲酸酯）和PEI 800 Da合成，形成PEI-Bu，可以在N/P比为38.35或以上的情况下缩合siRNA。纳米颗粒的尺寸为 100–300 nm，不同 N/P 比下的 Zeta 电位在 10–30 mV 范围内。纳米颗粒能够实现细胞摄取的能力，在稳定表达GL3荧光素酶基因的SMMC-7721细胞系中沉默效率约为46.63%。 MTT法检测，聚合物复合物纳米颗粒对SMMC-7721细胞的细胞毒性几乎可以忽略不计，表明荧光素酶表达的降低是RNAi的作用，而不是聚合物复合物细胞毒性的影响。将PEI-Bu和siRNA以N/P比115.05配制的复合物纳米颗粒局部注射到SMMC-7721荷瘤小鼠体内，与对照组相比，荧光素酶的表达量可降低至63.17%。这项研究的结果表明，PEI-Bu 聚阳离子可能为 siRNA 递送提供有前景的解决方案，并具有抗肿瘤基因治疗的潜力。
A challenge in gene therapy is the efficient delivery of DNA/siRNA to the diseased cells. The physicochemical characteristics of siRNA, such as high molecular weight, negative charges and hydrophilic nature—prevent passive diffusion across the plasma membrane for most cells. A therapeutically feasible carrier for intra-cellular delivery of gene materials should accomplish a series of tasks such as: condensing nucleic acid, protecting nucleic acid from leaking in vivo, facilitating endosome escape and releasing DNA/siRNA to the target site. To meet these requirements, an efficient gene vector based on polycation synthesis for siRNA delivery both in vitro and in vivo was developed. The polymer was synthesized by 1, 4-butanediol bis (chloroformate) and PEI 800 Da to form PEI-Bu which could condense siRNA at the N/P ratio of 38.35 or above. The size of the nanoparticles was 100–300 nm and zeta potential was in the range of 10–30 mV at different N/P ratios. The nanoparticles can achieve the ability of cellular uptake and the silencing efficiency was about 46.63% in SMMC-7721 cell line which was generated to stably express GL3 luciferase gene. The cytotoxicity of the polyplex nanoparticles was almost negligible on SMMC-7721 cells by MTT assay, indicating that the reduced luciferase expression was the effect of RNAi, not the influence of cytotoxicity of polyplexes. The polyplex nanoparticle formulated by PEI-Bu and siRNA at N/P ratio of 115.05 was injected into the SMMC-7721 tumor bearing mice locally and the expression of luciferase can reduce to 63.17% compared with control group. Results in this study suggested that PEI-Bu polycation might provide a promising solution for siRNA delivery and had the potential in anti-tumor gene therapy.
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双氨基甲酸酯交联低分子量 PEI 用于将 IL-1 受体拮抗剂基因递送至滑膜细胞以治疗关节炎
影响因子：
14
作者：
Xiang, Shengnan;Su, Jing;Zhang, Xiaoling
通讯作者：
Zhang, Xiaoling
影响因子：
64.8
作者：
Novina, CD;Sharp, PA
通讯作者：
Sharp, PA
DOI：
10.1016/j.ejpb.2004.11.011
发表时间：
2005-07-01
影响因子：
4.9
作者：
Lungwitz, U;Breunig, M;Göpferich, A
通讯作者：
Göpferich, A
影响因子：
4.9
作者：
Gao K;Huang L
通讯作者：
Huang L
DOI：
10.1038/nrd2742
发表时间：
2009-03
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Whitehead KA;Langer R;Anderson DG
通讯作者：
Anderson DG