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首页> 外文期刊>Oncology reports >Lung cancer gene therapy: Transferrin and hyaluronic acid dual ligand-decorated novel lipid carriers for targeted gene delivery
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Lung cancer gene therapy: Transferrin and hyaluronic acid dual ligand-decorated novel lipid carriers for targeted gene delivery

机译:肺癌基因治疗:转铁蛋白和透明质酸双配体装饰的新型脂质载体用于靶向基因递送

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摘要

To achieve lung cancer gene therapy, nanocarriers decorated with different ligands were used. Surface decoration and nanoparticulate system will assist in targeting the gene to specific cells and tissues, such as cancers and diseased organs. The aim of this research was to develop a dual ligand-decorated nanocarriers, which could target the tumor cells through receptor-mediated pathways to increase the uptake of genetic materials. Transferrin (Tf) and hyaluronic (HA) containing polyethylene glycoldistearoylphosphatidylethanolamine (Tf-PEG-DSPE and HA-PEG-DSPE) ligands were synthesized. Novel Tf and HA ligand-decorated, plasmid-enhanced green fluorescent protein loaded nanostructured lipid carriers (Tf/HA-pDNA NLC) was constructed. Physicochemical properties such as morphology, size, and zeta-potential as well as release properties were evaluated. The in vitro and in vivo gene transfection efficiency of Tf/HA-pDNA NLC was evaluated in lung adenocarcinoma A549 cells and lung cancer bearing animal models. Tf/HA-pDNA NLC displayed significantly higher transfection efficiency than undecorated DNA-NLCs and single ligand-decorated NLCs in vitro and in vivo. The newly constructed NLCs could successfully load gene; and Tf and HA functioned as excellent targeting ligands to improve the cell targeting ability of the gene-loaded nanocarriers. The resulting dual ligands decorated vectors could be a promising targeted gene delivery system for the lung cancer treatment.
机译:为了实现肺癌基因治疗,使用用不同配体装饰的纳米载体。表面装饰和纳米颗粒系统将有助于将基因靶向特异性细胞和组织,例如癌症和患病器官。本研究的目的是开发一种双配体装饰的纳米载体,其可以通过受体介导的途径靶向肿瘤细胞,以增加遗传物质的摄取。合成了含有聚乙二醇酯酰基氯胺(TF-PEG-DSPE和HA-PEG-DSPE)配体的转铁蛋白(TF)和透明质酸(HA)。构建了新型TF和HA配体装饰,质粒增强的绿色荧光蛋白负载纳米结构脂质载体(TF / HA-PDNA NLC)。评估了物理化学性质,如形态,大小和Zeta潜力以及释放性质。在肺腺癌A549细胞和肺癌轴承动物模型中评估了TF / HA-PDNA NLC的体外和体内基因转染效率。 TF / HA-PDNA NLC在体外和体内展示了比未污染的DNA-NLC和单一配体装饰的NLC显着更高的转染效率。新构建的NLC可以成功加载基因;和TF和HA用作优异的靶向配体,以改善基因负载纳米载体的细胞靶向能力。所得到的双配体装饰载体可能是肺癌治疗的有前途的靶向基因递送系统。

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