5 years ago

Construction of Polylysine Dendrimer Nanocomposites Carrying Nattokinase and their Application in Thrombolysis

Shaoyu Lü, Shaofei Zhang, Na Wen, Chunmei Gao, Mingzhu Liu, Xiubin Xu, Can Wu
Thrombotic disease has become one of the leading causes of mortality among humans globally. Nattokinase (NK), a novel thrombolytic agent, has attracted the attention of researchers. However, NK is a serine protease that is vulnerable to environmental effects resulting in its inactivation. In this study, polylysine dendrimer (PLLD) was synthesized via divergence-convergence method, and a series of NK/PLLD nanocomposites with different molar ratio was prepared. In addition, NK was successfully incorporated into the cores of PLLD G4 through hydrogen bonds and van der Waals forces. In NK/PLLD nanocomposites, when the molar ratio of NK to PLLD is 1:30, a high relative enzyme activity level (up to 117%) was achieved and was more stable at different temperatures and pH than free NK. In in vitro thrombolysis experiment, compared with free NK, NK/PLLD nanocomposites could control the release of NK. The thrombolysis rate of NK/PLLD nanocomposites reached 50% at 12 h, which can effectively avoid other complications such as hemorrhage. Interestingly, NK/PLLD nanocomposites with positive charge can penetrate into the negatively charged thrombus via electrostatic interaction, thus providing a good thrombolytic effect. Hemolysis and MTT experiments show that PLLD nanomaterials can serve as ideal carriers of protein drugs. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jbm.a.36232

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