Fabrication of zein-based hydrophilic nanoparticles for efficient gene delivery by layer-by-layer assembly

Fabrication of zein-based hydrophilic nanoparticles for efficient gene delivery by layer-by-layer assembly
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DOI:
10.1016/j.ijbiomac.2022.07.042
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发表时间:
2022-07-15
影响因子:
8.2
通讯作者:
Liu, Liang
Liu, Liang
中科院分区:
化学1区
文献类型:
--
作者:
Chen, Yiran;Liu, Chaobing;Liu, Liang

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玉米醇溶蛋白作为一种天然生物大分子,由于其独特的自组装特性,在药物递送方面具有广阔的应用前景。本工作采用pHcycle方法制备了玉米醇溶蛋白/海藻酸钠(Zein/SA)纳米复合材料,然后通过高效的层层组装方法制备了玉米醇溶蛋白/SA/PEI(ZSP)纳米复合材料,并进一步用叶酸(FA)标记了具有更高转染性能的ZSP纳米复合材料。通过各种方法表征 ZSP 的理化性质后,在体外探索了 ZSP 作为基因递送载体的潜力。结果表明,ZSP具有良好的分散性和稳定性,直径分布在124-203 nm范围内,具有典型的核壳结构,能有效凝聚DNA并保护其免受核酸酶水解。 ZSP具有与PEI相似的质子缓冲能力,比PEI具有更低的细胞毒性、更低的蛋白质吸附和红细胞溶血作用。 ZSP/pDNA复合物可以被细胞摄取,并且在相同重量比下比PEI/DNA复合物表现出更高的转染效率。通过FA标记可以提高复合物在HeLa和293T细胞中的转染效率,尤其是在HeLa细胞中。这些结果为设计和开发高效的基于玉米醇溶蛋白的基因传递系统提供了新的视角。
As a natural biological macromolecule, zein has broad application prospects in drug delivery due to its unique self-assembly properties. In this work, zein/sodium alginate (Zein/SA) nanocomposites were prepared by a pHcycle method, Then Zein/SA/PEI (ZSP) nanocomposites were prepared by efficient layer-by-layer assembly method, ZSP nanocomposite of higher transfection performance was further labeled by folic acid (FA). After characterizing the physicochemical properties of ZSP by various methods, the potential of ZSP as a gene delivery vehicle was explored in vitro. The results showed that ZSP had good dispersibility and stability, the diameter distribution was in the range of 124-203 nm, and it had a typical core-shell structure, which could effectively condensate DNA and protect it from nuclease hydrolysis. ZSP exhibited proton buffering capacity similar to PEI, lower cellular toxicity, lower protein adsorption and erythrocyte hemolysis effect than PEI. ZSP/pDNA complexes could be taken up by cells and exhibited higher transfection efficiency than PEI/DNA complexes at the same weight ratio. The transfection efficiency of the complex in HeLa and 293T cells can be improved by FA labeling, especially in HeLa cells. These results provide new perspective for the design and development of efficient zein-based gene delivery systems.