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Optimization of the Conditions for Plasmid DNA Delivery and Transfection with Self-Assembled Hyaluronic Acid-Based Nanoparticles
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-12-10 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00904 Hibah M Aldawsari 1 , Harkiranpreet Kaur Dhaliwal 2 , Bader Mubarak Aljaeid 1 , Nabil A. Alhakamy 1 , Zainy Mohammad Banjar 3 , Mansoor M. Amiji 2
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-12-10 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00904 Hibah M Aldawsari 1 , Harkiranpreet Kaur Dhaliwal 2 , Bader Mubarak Aljaeid 1 , Nabil A. Alhakamy 1 , Zainy Mohammad Banjar 3 , Mansoor M. Amiji 2
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Polymeric systems have been extensively studied as polyelectrolyte complexes to enhance the cellular delivery and transfection efficiency of genetic materials, such as plasmid DNA (pDNA). Here, self-assembled nanoparticles were formulated by complexation of hyaluronic acid (HA)-conjugated poly(ethylene glycol) (HA–PEG) and poly(ethylenimine) (HA–PEI), respectively, with pDNA creating relatively small, stable, and multifunctional nanoparticle complex formulations with high transfection efficiency. This formulation strategy offers high gene expression efficiency and negligible cytotoxicity in HeLa and A549 human lung cancer cell lines. To develop the ideal formulation, in vitro transfection efficiency was studied for three different nanoparticle formulations (HA–PEI/HA–PEG, HA–PEI, and HA–PEG) with different concentrations. The combination of the three polymers (HA, PEG, and PEI) was significant for the formulation to achieve the maximum gene expression results. The nanoparticles were found to be stable for up to a week at 4 °C conditions. Overall, these HA-based nanoparticles showed promising aspects that can be utilized in the designing of gene delivery vectors for cancer therapy.
中文翻译：
自组装透明质酸基纳米粒子的质粒DNA传递和转染条件的优化。
高分子系统已作为聚电解质复合物得到了广泛研究，以增强遗传物质（如质粒DNA（pDNA））的细胞传递和转染效率。在这里，通过将玻尿酸（HA）缀合的聚（乙二醇）（HA–PEG）和聚（乙炔亚胺）（HA–PEI）分别与pDNA络合，配制成自组装的纳米粒子，从而产生相对较小，稳定且稳定的pDNA。具有高转染效率的多功能纳米复合物配方。这种配制策略在HeLa和A549人肺癌细胞系中提供了高基因表达效率和微不足道的细胞毒性。为了开发理想的制剂，研究了三种不同浓度的不同纳米颗粒制剂（HA–PEI / HA–PEG，HA–PEI和HA–PEG）的体外转染效率。三种聚合物（HA，PEG和PEI）的组合对于实现最大的基因表达结果而言非常重要。发现纳米颗粒在4℃的条件下稳定长达一周。总体而言，这些基于HA的纳米颗粒显示出可用于癌症治疗的基因传递载体设计的有希望的方面。
更新日期：2018-12-10
中文翻译：
自组装透明质酸基纳米粒子的质粒DNA传递和转染条件的优化。
高分子系统已作为聚电解质复合物得到了广泛研究，以增强遗传物质（如质粒DNA（pDNA））的细胞传递和转染效率。在这里，通过将玻尿酸（HA）缀合的聚（乙二醇）（HA–PEG）和聚（乙炔亚胺）（HA–PEI）分别与pDNA络合，配制成自组装的纳米粒子，从而产生相对较小，稳定且稳定的pDNA。具有高转染效率的多功能纳米复合物配方。这种配制策略在HeLa和A549人肺癌细胞系中提供了高基因表达效率和微不足道的细胞毒性。为了开发理想的制剂，研究了三种不同浓度的不同纳米颗粒制剂（HA–PEI / HA–PEG，HA–PEI和HA–PEG）的体外转染效率。三种聚合物（HA，PEG和PEI）的组合对于实现最大的基因表达结果而言非常重要。发现纳米颗粒在4℃的条件下稳定长达一周。总体而言，这些基于HA的纳米颗粒显示出可用于癌症治疗的基因传递载体设计的有希望的方面。
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