Enhancing the in vivo stability of polycation gene carriers by using PEGylated hyaluronic acid as a shielding system

Jiaxue Liu, Xiaoli Bao, I. Kolesnik, Boyan Jia, Zihan Yu, Caiyun Xing, Jiawen Huang, Tingting Gu, Xiaotong Shao, Alexey Kletskov, A. Kritchenkov, V. Potkin, Wenliang Li
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引用次数: 15

Abstract

To increase the in vivo stability of cationic gene carriers and avoid the adverse effects of their positive charge, we synthesized a new shielding material by conjugating low molecular weight polyethylene glycol (PEG) to a hyaluronic acid (HA) core. The HA-PEG conjugate assembled with the positively charged complex, forming a protective layer through electrostatic interactions. DNA/polyetherimide/HA-PEG (DNA/PEI/HA-PEG) nanoparticles had higher stability than both DNA/polyethyleneimine (DNA/PEI) and DNA/PEI/HA complexes. Furthermore, DNA/PEI/HA-PEG nanoparticles also showed a diminished nonspecific response toward serum proteins in vivo. The in vivo transfection efficiency was also enhanced by the low cytotoxicity and the improved stability; therefore, this material might be promising for use in gene delivery applications.
聚乙二醇化透明质酸作为屏蔽体系增强多阳离子基因载体的体内稳定性
为了提高阳离子基因载体在体内的稳定性,避免其正电荷的不利影响,我们将低分子量聚乙二醇(PEG)偶联到透明质酸(HA)核上,合成了一种新的屏蔽材料。HA-PEG偶联物与带正电的配合物组装,通过静电相互作用形成保护层。DNA/聚醚亚胺/HA- peg (DNA/PEI/HA- peg)纳米颗粒的稳定性高于DNA/聚乙烯亚胺(DNA/PEI)和DNA/PEI/HA配合物。此外,DNA/PEI/HA-PEG纳米颗粒在体内对血清蛋白的非特异性反应也有所减弱。低细胞毒性和稳定性提高了体内转染效率;因此,这种材料可能在基因传递应用中有很大的前景。
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CiteScore
5.40
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