Highly efficient cationic hydroxyethylated cholesterol-based nanoparticle-mediated gene transfer in vivo and in vitro in prostate carcinoma PC-3 cells
Highly efficient cationic hydroxyethylated cholesterol-based nanoparticle-mediated gene transfer in vivo and in vitro in prostate carcinoma PC-3 cells
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DOI：
10.1016/j.jconrel.2007.04.012
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发表时间：
2007-07-13
影响因子：
10.8
通讯作者：
Maitani, Yoshie
中科院分区：
文献类型：
--
作者：
Hattori, Yoshiyuki;Ding, Wu-xiao;Maitani, Yoshie
最佳的肿瘤基因治疗必须以高效率和最小的毒性将DNA传递到肿瘤细胞。据报道，在非病毒基因传递中，阳离子脂质氨基末端的羟基乙基对高转染效率至关重要。因此，在本研究中，我们开发了由胆固醇-3 β -羧基酰胺-乙烯- n-羟乙胺和Tween 80组成的新型阳离子纳米颗粒（NP-OH），并优化了体外和体内转染，作为人类前列腺肿瘤PC-3细胞和异种移植物的非病毒DNA载体。在氯化钠（NaCl）存在的条件下制备带正电荷的纳米复合物，体外转染可实现高效的DNA转移。在体内转染时，在水中形成的带负电荷的纳米复合物比直接转染到异种移植物时形成的带正电荷的纳米复合物更能诱导基因表达。这些转染效率在体外和体内是相当的每一个商业产品。此外，NP-OH纳米复合物在静脉注射时没有诱导肿瘤坏死因子(TNF)- α。实验结果为形成NP-OH纳米复合物提供了体外和体内基因传递的最佳条件。NP-OH是一种潜在的非病毒DNA载体，可用于肿瘤的局部治疗和体外治疗。(C) 2007 Elsevier B.V.版权所有
Optimal gene therapy for tumors must deliver DNA to tumor cells with high efficiency and minimal toxicity. It has been reported that in nonviral gene delivery, the hydroxyethyl group at the amino terminal in cationic lipid was important for high transfection efficiency. Therefore, in this study, we developed new cationic nanoparticles (NP-OH) composed of cholesteryl-3 beta-carboxyamidoethylene-N-hydroxyethylamine and Tween 80, and optimized in vitro and in vivo transfections for potential use as a non-viral DNA vector into human prostate tumor PC-3 cells and xenografts.' In vitro transfection resulted in efficient DNA transfer when positive-charged nanoplex was prepared in the presence of sodium chloride (NaCl). In in vivo transfection, negative-charged nanoplex formed in water strongly induced the gene expression compared with positive-charged nanoplex when directly transfected into xenografts. These transfection efficiencies in vitro and in vivo were comparable to each commercial product. Furthermore, NP-OH nanoplexes displayed no induction of tumor necrosis factor (TNF)-alpha when administered by intravenous injection. The results of the experiments provided optimal conditions to form NP-OH nanoplex for gene delivery in vitro and in vivo. NP-OH is a potential non-viral DNA vector for the local treatment of tumor and in vitro. (C) 2007 Elsevier B.V. All rights reserved.