Biocompatibility characteristics of the metal organic framework ZIF-8 for therapeutical applications
Biocompatibility characteristics of the metal organic framework ZIF-8 for therapeutical applications
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DOI：
10.1016/j.apmt.2017.12.014
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发表时间：
2018-06-01
影响因子：
8.3
通讯作者：
Pane, Salvador
中科院分区：
文献类型：
--
作者：
Hoop, Marcus;Walde, Claudio F.;Pane, Salvador
金属有机骨架(MOF)是由有机连接物和无机结点构成的一类晶体材料。MOF通常具有超高的表面积和孔容，因此，它们是生物医学应用的理想候选者。咪唑锌骨架8(ZIF-8)作为一种潜在的按需给药应用，在文献中已被广泛建立。事实上，ZIF-8具有显著的负载能力、在生理环境中的稳定性以及可调的药物释放特性。然而，将ZIF-8用于体内应用需要清楚地了解ZIF-8与生物组织的相互作用。在这项工作中，我们研究了ZIF-8对代表身体不同部位(肾脏、皮肤、乳房、血液、骨骼和结缔组织)的六种不同细胞系的生物相容性。我们的结果表明，ZIF-8在30微克毫升(-1)的阈值下没有明显的细胞毒性。在30微克毫克毫升(-1)以上，细胞毒性是由于释放的锌离子(锌离子)影响线粒体ROS的产生。这种不利的影响是由于不可逆转的DNA损伤导致细胞周期停滞在G2/M期，最终启动细胞凋亡途径。基于这一认识，我们将一种激素胰岛素封装到ZIF-8颗粒中，然后将其药物输送能力与前述细胞毒性值进行比较。我们的结果表明，ZIF-8适合于治疗应用。此外，这项研究建立了对ZIF-8及其成分与各种细胞系相互作用的明确理解，并强调了未来体内测试必须考虑的重要生物相容性因素。(C)2017爱思唯尔有限公司。保留所有权利。
Metal-organic frameworks (MOFs) are a class of crystalline materials constructed from organic linkers and inorganic nodes. MOFs typically possess ultra-high surface areas and pore volumes; thus, they are ideal candidates for biomedical applications. Zinc Imidazolate Framework 8 (ZIF-8) has been widely established in the literature as a potential candidate for on-demand drug delivery applications. Indeed, ZIF-8 has a remarkable loading capacity, stability in physiological environments, and tunable drug release properties. However, the use of ZIF-8 for in vivo applications requires a clear understanding of the interaction of ZIF-8 with biological tissue. In this work, we investigated the biocompatibility of ZIF-8 toward six different cell lines representing various body parts (kidney, skin, breast, blood, bones, and connective tissue). Our results suggest that ZIF-8 has no significant cytotoxicity up to a threshold value of 30 mu g mL(-1). Above 30 mu g mL(-1), the cytotoxicity is shown to result from the influence of released Zinc ions (Zn2+) on the mitochondrial ROS production. This adverse effect is responsible for cell cycle arrest in the G2/M phase due to irreversible DNA damage, ultimately initiating cellular apoptosis pathways. Due to this insight, we encapsulated a hormone, insulin, into ZIF-8 particles and then compared its drug delivery capabilities to the aforementioned cytotoxicity values. Our results suggest that ZIF-8 is suitable for therapeutic applications. Furthermore, this study establishes a clear understanding of the interaction of ZIF-8 and its constituents with various cell lines and highlights the important biocompatibility factors that must be considered for future in vivo testing. (C) 2017 Elsevier Ltd. All rights reserved.