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使用双特异性适体进行双向酶抑制和激活以原位形成可注射水凝胶。

Bidirectional Enzyme Inhibition and Activation for In Situ Formation of Injectable Hydrogel Using a Bispecific Aptamer.

作者信息

Wen Connie, Lee Kyungsene, Wang Yixun, Wang Xuelin, Wang Yong

机构信息

Department of Biomedical Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.

出版信息

Langmuir. 2024 Dec 17;40(50):26751-26759. doi: 10.1021/acs.langmuir.4c03925. Epub 2024 Dec 6.

DOI:10.1021/acs.langmuir.4c03925
PMID:39642164
Abstract

In situ injectable hydrogels have been explored for biomedical applications, including regenerative medicine and drug delivery. However, controlling the kinetics of their gelation to facilitate easy injection remains a challenge. The purpose of this study was to demonstrate the potential of using bispecific aptamers and complementary sequences as a bidirectional modulation system for controlling enzyme-mediated hydrogel formation kinetics. The results show that a bispecific thrombin-binding aptamer effectively inhibits thrombin activity and significantly slowed fibrin hydrogel formation. Upon interaction with its complementary sequence, this inhibition could be reversed. As a result, the aptamer-bound thrombin was activated, leading to an acceleration of the fibrin formation kinetics. Thus, bispecific aptamers and complementary sequences can effectively function as dynamic control systems for enzyme-catalyzed in situ injectable hydrogel formation.

摘要

原位可注射水凝胶已被用于生物医学应用,包括再生医学和药物递送。然而,控制其凝胶化动力学以便于注射仍然是一个挑战。本研究的目的是证明使用双特异性适配体和互补序列作为双向调节系统来控制酶介导的水凝胶形成动力学的潜力。结果表明,双特异性凝血酶结合适配体有效地抑制了凝血酶活性,并显著减缓了纤维蛋白水凝胶的形成。与其互补序列相互作用后,这种抑制作用可以逆转。结果,与适配体结合的凝血酶被激活,导致纤维蛋白形成动力学加速。因此,双特异性适配体和互补序列可以有效地作为酶催化原位可注射水凝胶形成的动态控制系统。

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Bidirectional Enzyme Inhibition and Activation for In Situ Formation of Injectable Hydrogel Using a Bispecific Aptamer.使用双特异性适体进行双向酶抑制和激活以原位形成可注射水凝胶。
Langmuir. 2024 Dec 17;40(50):26751-26759. doi: 10.1021/acs.langmuir.4c03925. Epub 2024 Dec 6.
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DNA-triggered activation of aptamer-neutralized enzyme for formation of injectable hydrogel.DNA触发的适配体中和酶激活以形成可注射水凝胶。
Nanoscale Horiz. 2025 Jul 21;10(8):1703-1716. doi: 10.1039/d5nh00314h.