聚乙二醇化鱼精蛋白基吸附提高了四面体骨架核酸的生物学特性和稳定性。,ACS Applied Materials & Interfaces

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聚乙二醇化鱼精蛋白基吸附提高了四面体骨架核酸的生物学特性和稳定性。
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2019-07-24 , DOI: 10.1021/acsami.9b09243
Yichen Ge ₁ , Taoran Tian ₁ , Xiaoru Shao ₁ , Shiyu Lin ₁ , Tao Zhang ₁ , Yunfeng Lin ₁ , Xiaoxiao Cai ₁

Affiliation

最近，许多研究人员报告说，DNA纳米结构（如四面体框架核酸（tFNA））具有可编程形状，功能位点和生物学响应，因此在临床和实验室应用中具有很大的潜力成为有用的工具。然而，由于各种不利因素，有限的内吞作用和细胞和体液中的稳定性损害了DNA纳米结构的功能。在这项研究中，我们成功地合成了聚乙二醇化鱼精蛋白，并且以适当比例的鱼精蛋白中的氮与tFNAs中的磷（N / P比）作为功能复合物吸附了tFNAs。此外，我们证明了聚乙二醇化鱼精蛋白吸附的tFNAs比裸露的tFNAs对细胞活力和增殖表现出更突出的积极作用。可以在带有PEG-鱼精蛋白-tFNA（PPT）复合物的三个不同组织来源的细胞中观察到内吞作用的增加。内吞能力的提高是由多种途径介导的。此外，通过抑制小窝依赖性途径极大地阻断了PPT复合物对内吞能力的刺激作用。一致地，当tFNA被PEG化鱼精蛋白稳定时，它们通常倾向于从溶酶体中逃逸并在生物体液中存活更长的时间，而不是从肾脏中迅速清除。我们研究的体外和体内结果表明，PPT复合法是一种可行，有效且低成本的策略，可改善tFNA的生物相容性，稳定性和内在化。

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PEGylated Protamine-Based Adsorbing Improves the Biological Properties and Stability of Tetrahedral Framework Nucleic Acids.

Recently, many researchers have reported that DNA nanostructures, such as tetrahedral framework nucleic acids (tFNAs), have great potential to be useful tools in clinical and laboratory applications due to their programmable shapes, functional sites, and biological responses. However, finite endocytosis and stability in cells and body fluids compromise the functions of DNA nanostructures as a result of various adverse factors. In this study, we successfully synthesized PEGylated protamine, and tFNAs were adsorbed to it in a proper ratio of nitrogen in protamine to phosphorus in tFNAs (N/P ratio) as the functional complex. Furthermore, we demonstrated that PEGylated protamine-adsorbed tFNAs show a more prominent positive effect on cell viability and proliferation than naked tFNAs do. An increase in endocytosis can be observed in three different tissue-derived cells with the PEG-protamine-tFNA (PPT) complex. The increased endocytic ability is mediated by multiple pathways; moreover, the stimulatory effect of the PPT complex on the endocytic ability is dramatically blocked by the inhibition of the caveola-dependent pathway. Consistently, when tFNAs are stabilized by PEGylated protamine, they often tend to escape from lysosomes and survive for a longer period in biological fluids rather than being rapidly eliminated from the kidneys. The in vitro and in vivo results of our study demonstrate that the PPT complex method is a feasible, potent, and low-cost strategy that improves tFNA biocompatibility, stability, and internalization. This study provides evidence supporting the possibility of implementing PPTs for use in drug delivery, bioimaging, and gene transfection in the future.

更新日期：2019-07-12

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