Lin Jiansheng, Huang Linghong, Ou Haibo, Chen An, Xiang Rong, Liu Zonghua
Department of Anatomy, Hunan University of Chinese Medicine Changsha 410208 China.
Department of Biomedical Engineering, Jinan University Guangzhou 510632 China
RSC Adv. 2021 Jun 16;11(35):21414-21425. doi: 10.1039/d1ra02873a. eCollection 2021 Jun 15.
ZIF-8 MOFs, with their large specific surface area and void volume, unique biodegradability and pH sensitivity, and significant loading capacity, have been widely used as carrier materials for bioactive molecules such as drugs, vaccines and genes. In these applications, ZIF-8 MOFs are usually delivered intravenously. Therefore, it is necessary to know the interaction between ZIF-8 MOFs and blood components, which from this sense is a key factor affecting their delivery effectiveness and biosafety. However, until now there has been no report on the evaluation of hemocompatibility of ZIF-8 MOFs. The lack of biosafety information of ZIF-8 MOFs seriously impedes their clinical applications. In this work, we studied the biosafety of two different sizes of ZIF-8 MOFs, mainly focusing on their and effects on the key components of blood (red blood cells (RBCs), platelets, ) and the coagulation function. It was found that, , a high concentration of ZIF-8 MOFs could induce RBC aggregation and hemolysis, and prolong the coagulation time. , intravenous administration of 45 mg kg ZIF-8 MOFs significantly disturbed the RBC and platelet-related blood routine indexes, as well as coagulation function indexes, but it did not cause significant abnormalities in blood coagulation and tissue structures (heart, liver, spleen, lung, and kidney).
具有大比表面积和孔隙体积、独特的生物可降解性和pH敏感性以及显著负载能力的ZIF-8金属有机框架材料，已被广泛用作药物、疫苗和基因等生物活性分子的载体材料。在这些应用中，ZIF-8金属有机框架材料通常通过静脉给药。因此，有必要了解ZIF-8金属有机框架材料与血液成分之间的相互作用，从这个意义上讲，这是影响其给药效果和生物安全性的关键因素。然而，迄今为止，尚未有关于ZIF-8金属有机框架材料血液相容性评估的报道。ZIF-8金属有机框架材料缺乏生物安全性信息严重阻碍了它们的临床应用。在这项工作中，我们研究了两种不同尺寸的ZIF-8金属有机框架材料的生物安全性，主要关注它们对血液关键成分（红细胞（RBCs）、血小板）的影响以及凝血功能。结果发现，高浓度的ZIF-8金属有机框架材料会诱导红细胞聚集和溶血，并延长凝血时间。此外，静脉注射45mg/kg的ZIF-8金属有机框架材料会显著干扰与红细胞和血小板相关的血常规指标以及凝血功能指标，但不会导致凝血和组织结构（心脏、肝脏、脾脏、肺和肾脏）出现明显异常。
