Preparation and cell activities of lactosylated curdlan-triornithine nanoparticles for enhanced DNA/siRNA delivery in hepatoma cells

Preparation and cell activities of lactosylated curdlan-triornithine nanoparticles for enhanced DNA/siRNA delivery in hepatoma cells
复制标题

用于增强肝癌细胞中 DNA/siRNA 递送的乳糖基化凝胶多糖-三鸟氨酸纳米颗粒的制备和细胞活性

DOI:
10.1016/j.carbpol.2019.115252
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发表时间:
2019-12-01
影响因子:
11.2
通讯作者:
Han, Jingfen
Han, Jingfen
中科院分区:
化学1区
文献类型:
--
作者:
Wang, Xia;Qi, Yuxuan;Han, Jingfen

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期待已久的癌症治疗将向靶标提供正确类型的治疗药物并加以控制,同时将全身毒性降至最低。本研究的目的是制备乳糖基化凝胶多糖-三鸟氨酸纳米载体(CTOLs),并将基因靶向递送至肝癌细胞。结构和生物物理性质已通过物理和化学方法阐明。结果表明,这些功能化聚合物可以将基因完全浓缩成球形纳米颗粒。依次进行细胞毒性实验、GFP-pDNA和siRNA体外转染。观察结果显示,乳糖酸取代度最高的CTOL 20%将基因靶向递送至过度表达ASGPR受体的HepG2细胞中,并具有超过70%的良好基因敲除效率。同时,载体表现出优异的生物相容性。我们的研究表明,具有较低毒性和较高基因结合能力的 CTOL 可以作为一个潜在的有价值的平台,可以针对肝癌细胞进行定制治疗基因。
A long-anticipated cancer therapy would deliver the right type of therapeutic agents to the target in control with minimal systemic toxicity. The purpose of this study was to prepare lactosylated curdlan-triornithine nano-carriers (CTOLs), and target deliver gene to hepatoma cells. Structures and biophysical properties had been elucidated with physical and chemical methods. The results revealed that those functionalized polymers can completely condense the gene into spherical nanoparticles. Cytotoxicity assay, GFP-pDNA and siRNA transfecfion in vitro were implemented successively. Observations showed that CTOL 20% with the highest lactose acid substitution degree targeted delivered gene into HepG2 cells over expressing ASGPR receptors and had pretty gene knockdown efficiency over 70%. Meanwhile, the carriers showed excellent biocompatibility. Our studies demonstrated that CTOLs with lower toxicity and higher gene binding capacity may serve as a potential valuable platform that can be tailored to target the liver cancer cells for therapeutic gene.