Simulation and Experimental Assembly of DNA-Graft Copolymer Micelles with Controlled Morphology.

Simulation and Experimental Assembly of DNA-Graft Copolymer Micelles with Controlled Morphology.
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DOI:
10.1021/acsbiomaterials.5b00080
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发表时间:
2015-06-08
影响因子:
5.8
通讯作者:
Luijten E
Luijten E
中科院分区:
工程技术2区
文献类型:
--
作者:
We Z;Ren Y;Williford JM;Qu W;Huang K;Ng S;Mao HQ;Luijten E

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通过与质粒DNA和共聚物络合形成的纳米颗粒是一种很有前途的基因递送载体,与其他递送策略相比具有广泛的优势。值得注意的是,最近的研究表明,这些颗粒的形状可以调节,这使得了解它们的形状依赖的转染性成为可能。尽管早期的方法是通过使用嵌段共聚物和改变溶剂极性来实现形状调节的,但在这里,我们通过实验和计算相结合的方法证明了通过使用更容易合成的接枝共聚物来实现相同程度的形状控制,并为形状控制提供了更广泛的参数范围。此外,本文提出的方法不需要使用有机溶剂。该模拟工作不仅为进一步设计非病毒基因传递载体提供了一个有效的模型,而且也为控制形状变化的机制提供了洞察力。我们的实验结果为简单、大规模地合成具有良好控制的形状和可调的转染性的生物相容的基因传递载体提供了重要的机会。体外研究表明,胶束形状和转染率都与接枝共聚物载体的关键结构参数密切相关。
Nanoparticles formed through complexation of plasmid DNA and copolymers are promising gene-delivery vectors, offering a wide range of advantages over alternative delivery strategies. Notably, recent research has shown that the shape of these particles can be tuned, which makes it possible to gain understanding of their shape-dependent transfection properties. Whereas earlier methods achieved shape tuning through the use of block copolymers and variation of solvent polarity, here we demonstrate through a combined experimental and computational approach that the same degree of shape control can be achieved through the use of graft copolymers that are easier to synthesize and provide a wider range of parameters for shape control. Moreover, the approach presented here does not require the use of organic solvents. The simulation work provides insight into the mechanism governing the shape variation as well as an effective model to guide further design of non-viral gene-delivery vectors. Our experimental findings offer important opportunities for the facile and large-scale synthesis of biocompatible gene-delivery vectors with well-controlled shape and tunable transfection properties. The in vitro study shows that both micelle shape and transfection efficiency are strongly correlated with the key structural parameters of the graft copolymer carriers.
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