Enhanced in vitro DNA transfection efficiency by novel folate-linked nanoparticles in human prostate cancer and oral cancer
Enhanced in vitro DNA transfection efficiency by novel folate-linked nanoparticles in human prostate cancer and oral cancer
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DOI：
10.1016/j.jconrel.2004.03.007
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发表时间：
2004-05-31
影响因子：
10.8
通讯作者：
Maitani, Y
中科院分区：
文献类型：
--
作者：
Hattoni, Y;Maitani, Y
开发并评价了新型叶酸连接的阳离子纳米颗粒（NP）用于向人口腔癌（KB细胞）和人前列腺癌（LNCaP细胞）基因递送的潜在用途，所述人口腔癌（KB细胞）和人前列腺癌（LNCaP细胞）大量表达叶酸结合蛋白。将叶酸-聚乙二醇-二硬脂酰磷脂酰乙醇胺缀合物（f-PEG-DSPE）掺入由3（[N-（N，N '-二甲基氨基乙烷）-氨基甲酰基]胆固醇（DC-Chol）和吐温80组成的NP中。NP-0.3FT、-1FT和-1FLT分别含有0.3和1 mol% f-PEG（2000）-DSPE和1 mol % f-PEG（5000）-DSPE，显示出约100-200 nm的尺寸。NP/质粒DNA复合物（nanoplex）保持在可注射尺寸（230-340 nm），并且在血清中略微增加其尺寸。NP-1FT与KB细胞的结合被f-PEG 2000-DSPE增强，并被与培养基中的游离叶酸共孵育所阻断。在转染活性方面，NP-1FT在血清存在下对KB和LNCaP细胞显示出高活性，而NP-1FLT没有。NP-0.3FT在LNCaP细胞中也显示出高活性，但在KB细胞中没有。RT-PCR分析显示，KB细胞强烈表达叶酸受体mRNA，而LNCaP细胞不表达。相反，LNCaP细胞表达前列腺特异性膜抗原（PSMA）的mRNA，其与叶酸底物相互作用。LNCaP细胞中叶酸连接的NPs的摄取机制可能与KB细胞中的摄取机制不同。这是叶酸连接的NP选择性地将DNA递送到LNCaP细胞的第一份报告，表明这种NP是潜在的前列腺癌基因递送靶向载体。(C)2004 Elsevier B. V.保留所有权利。
Novel folate-linked, cationic nanoparticles (NPs) were developed and evaluated for potential use for gene delivery to human oral cancer (KB cells) and human prostate cancer (LNCaP cells), which abundantly expressed folate binding proteins. Folate-polyethylenglycol-distearoylphosphatidylethanolamine conjugate (f-PEG-DSPE) was incorporated in NPs composed of 3([N-(N,N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and Tween 80. NP-0.3FT, -1FT and -1FLT, which contain 0.3 and 1 mol% f-PEG(2000)-DSPE, and 1 mol% f-PEG(5000)-DSPE, respectively, showed about 100-200 nm in size. The NP/plasmid DNA complex (nanoplex) remained in an injectable size (230-340 nm) and slightly increased its size in serum. The association of NP-1FT with KB cells was enhanced by f-PEG2000-DSPE and was blocked by co-incubation with free folic acid in medium. In transfection activity, the NP-1FT, but not NP-1FLT, showed high activity into KB and LNCaP cells in the presence of serum. The NP-0.3FT also showed high activity into LNCaP cells, but not KB cells. In RT-PCR analysis, KB cells strongly expressed folate receptors mRNA, but LNCaP cells did not. In contrast, LNCaP cells expressed mRNA of prostate-specific membrane antigen (PSMA), which interacts with the folate substrate. Uptake mechanism of folate-linked NPs in LNCaP cells may be different from that in KB cells. This is the first report that folate-linked NPs selectively deliver the DNA to LNCaP cells, suggesting that such NPs are potentially targeted vectors to prostate cancer for gene delivery. (C) 2004 Elsevier B.V. All rights reserved.