Lipid-Coated Gold Nanoparticles Functionalized by Folic Acid as Gene Vectors for Targeted Gene Delivery in vitro and in vivo
Lipid-Coated Gold Nanoparticles Functionalized by Folic Acid as Gene Vectors for Targeted Gene Delivery in vitro and in vivo
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DOI：
10.1002/cmdc.201700391
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发表时间：
2017-11-08
期刊：
影响因子：
3.4
通讯作者：
Wang, Jin
中科院分区：
文献类型：
--
作者：
Du, Baoji;Gu, Xiaoxiao;Wang, Jin
脂质纳米粒作为基因载体以其高的基因转染效率和低的细胞毒性而备受关注。在我们之前的工作中，我们合成了金纳米颗粒/二甲基双十八烷基溴化铵（DODAB）/二油酰磷脂酰乙醇胺（DOPE）（GDD）作为阴离子脂质和pH敏感的基因载体。为了进一步实现靶向基因转染，制备了一系列具有不同DOPE-FA比例的金纳米颗粒/ DODAB/DOPE/DOPE-叶酸（DOPE-FA），并将其命名为GFn（其中n=1.0、2.5、5.0、7.5或10.0%）。GF 2.5介导的基因转染效率在MCF-7（FA受体阳性细胞）中可达85%左右，高于阴性对照（GDD，35%）和阳性对照（Lipofectamine 2000，65%）。然而，GF2.5不能进一步促进基因转染入A549（FA受体阴性细胞）。MCF-7细胞的较高基因转染效率可归因于由FA靶向能力介导的增强的细胞摄取效率。此外，还发现GF2.5在特定的肿瘤部位积聚，并显示出增强的体内基因递送能力。此外，在用GF2.5处理后，未观察到对小鼠的主要组织的显著损害。因此，GF2.5具有靶向性和提高的转染效率，显示了其在过表达FA受体的肿瘤细胞的基因治疗中的应用前景。我们相信，本研究的结果将在基因治疗中找到更广泛的应用。
Lipid-based nanoparticles as gene vectors have attracted considerable attention for their high gene transfection efficiency and low cytotoxicity. In our previous work, we synthesized gold nanoparticles/dimethyldioctadecylammonium bromide (DODAB)/dioleoylphosphatidylethanolamine (DOPE) (GDD) as anionic lipid-and pH-sensitive gene vectors. To further realize targeted gene transfection, a series of gold nanoparticles/ DODAB/DOPE/DOPE-folic acid (DOPE-FA) with various ratios of DOPE-FA were prepared and termed as GFn (for which n=1.0, 2.5, 5.0, 7.5, or 10.0 %). The gene transfection efficiency mediated by GF2.5 can reach about 85% for MCF-7 (FA-receptor-positive cells), higher than those of the negative control (GDD, 35%) and positive control (Lipofectamine 2000, 65 %). However, GF2.5 does not further promote gene transfection into A549 (FA-receptor-negative cells). The higher gene transfection efficiency for MCF-7 cells can be attributed to enhanced cellular uptake efficiency mediated by the FA targeting ability. Furthermore, GF2.5 was also found to accumulate at the specific tumor site and showed enhanced in vivo gene delivery ability. In addition, no significant harm was observed for the main tissues of the mice after treatment with GF2.5. Therefore, GF2.5, with the targeting ability and improved transfection efficiency, shows promise for its utility in gene therapy for tumor cells that overexpress FA receptors. We believe the results of this study will find more broad applications in gene therapy.