Hydrophobic poly (amino acid) modified PEI mediated delivery of rev-casp-3 for cancer therapy
Hydrophobic poly (amino acid) modified PEI mediated delivery of rev-casp-3 for cancer therapy
复制标题
疏水性聚（氨基酸）修饰的 PEI 介导 rev-casp-3 的递送用于癌症治疗。
DOI：
10.1016/j.biomaterials.2012.02.057
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发表时间：
2012-06-01
期刊：
影响因子：
14
通讯作者：
Chen, Xuesi
中科院分区：
文献类型：
--
作者：
Fu, Chunling;Lin, Lin;Chen, Xuesi
最近的研究表明，两亲性阳离子聚合物具有作为基因载体的潜力，在体外环境中具有高转染效率和低细胞毒性，以递送药物、siRNA和质粒DNA。然而，它们在体内的安全性和有效性仍然是一个挑战，需要进一步的研究。在我们之前的工作中，PP 80作为一种新型的两亲性阳离子聚合物通过将疏水聚苯丙氨酸片段接枝到PEI上而合成，其在体外许多细胞系中显示出比PEI更高的转染效率。本文报道了PP 80/pDNA复合物在体内外均表现出良好的生物相容性。此外，当治疗性基因rev-casp-3与PP 80缀合并瘤内施用至HeLa异种移植物模型时，诱导显著的肿瘤凋亡，同时抑制肿瘤生长，表明PP 80介导实体瘤中rev-casp-3基因的表达，对荷瘤小鼠没有可检测的副作用。这些数据表明，PP 80作为一种有前途的癌症基因递送载体值得进一步研究。(C)2012爱思唯尔有限公司保留所有权利。
Recent studies in amphiphilic cationic polymers have demonstrated their potential as gene carriers with high transfection efficiency and low cytotoxicity in the in vitro settings to deliver drug, siRNA and plasmid DNA. Yet their safety and efficacy in vivo remain to be a challenge, and require further investigation. In our previous work, PP80 was synthesized as a novel amphiphilic cationic polymer by grafting hydrophobic polyphenylalanine segment on PEI, which displayed higher transfection efficiency than PEI in a number of cell lines in vitro. Here, we reported the favorable biocompatibility displayed by PP80/pDNA complex both in vitro and in vivo. Furthermore, when therapeutic gene rev-casp-3 was conjugated to PP80 and administered intratumorally to a HeLa xenograft model, significant tumor apoptosis was induced with concurrent tumor growth inhibition, indicating that PP80 mediated expression of rev-casp-3 gene in solid tumors with not detectable side effects on the tumor-bearing mice. These data demonstrated that PP80 warrants further investigation as a promising cancer gene delivery vehicle. (C) 2012 Elsevier Ltd. All rights reserved.