Dongguan Children's Hospital; School of Pharmacy, Guangdong Medical University, Dongguan 523000, China.
Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE, Shandong Key Laboratory of Biochemical Analysis, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, China.
Int J Biol Macromol. 2024 Nov;281(Pt 1):136212. doi: 10.1016/j.ijbiomac.2024.136212. Epub 2024 Oct 2.
Protamine (PA) is the only licensed antidote for reversing heparin anticoagulation by electrostatically binding with heparin. Efforts have been made on designing various heparin-scavengers, while, it remains a great challenge for gaining the external-stimuli responsive PA-release material. In this study, a generic strategy is developed for fabricating photoresponsive protein materials with the designed azobenzene-containing surfactant. For the first time, based on the isomerization of azobenzene, both cationic and anionic proteins could be phase change biomaterials which are capable of transiting to isotropic state under UV irradiation at room temperature. The formation of isotropic state could set the proteins free from the binding state, activating their intrinsic biological functions. Employing this mechanism, one smart PA material for inhibiting heparin is developed, which could effectively photo-modulate the heparin concentration by turning on-and-off the free state of PA from the binding state. With good biocompatibility, the PA material addresses photoresponsive hemostatic activity in biological studies, confirming its great potential clinical values. This work provides a new designing strategy for gaining photocontrollable hemostasis materials, also opening new opportunities for developing photoresponsive protein drugs and biomedical materials.
鱼精蛋白(PA)是唯一被批准的逆转肝素抗凝作用的解毒剂,通过静电与肝素结合。虽然已经在设计各种肝素清除剂方面做出了努力,但获得对外界刺激有响应的 PA 释放材料仍然是一个巨大的挑战。在这项研究中,开发了一种通用策略,用于制造具有设计的含偶氮苯表面活性剂的光响应蛋白材料。首次基于偶氮苯的异构化,阳离子和阴离子蛋白都可以成为各向同性的相变生物材料,能够在室温下通过紫外线照射转变为各向同性状态。各向同性状态的形成可以使蛋白质从结合状态中释放出来,激活其内在的生物学功能。利用这一机制,开发了一种用于抑制肝素的智能 PA 材料,它可以通过打开和关闭 PA 从结合状态到游离状态,有效地对肝素浓度进行光调节。该 PA 材料具有良好的生物相容性,在生物研究中解决了光响应止血活性的问题,证实了其具有巨大的潜在临床价值。这项工作为获得光控止血材料提供了一种新的设计策略,也为开发光响应蛋白药物和生物医学材料开辟了新的机会。