Faizan Muhammad, Muhammad Niaz, Niazi Kifayat Ullah Khan, Hu Yongxia, Wang Yanyan, Wu Ya, Sun Huaming, Liu Ruixia, Dong Wensheng, Zhang Weiqiang, Gao Ziwei
Key Laboratory of Applied Surface and Colloid Chemistry MOE, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710062, China.
Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China.
Materials (Basel). 2019 May 20;12(10):1643. doi: 10.3390/ma12101643.
The CO-releasing materials (CORMats) are used as substances for producing CO molecules for therapeutic purposes. Carbon monoxide (CO) imparts toxic effects to biological organisms at higher concentration. If this characteristic is utilized in a controlled manner, it can act as a cell-signaling agent for important pathological and pharmacokinetic functions; hence offering many new applications and treatments. Recently, research on therapeutic applications using the CO treatment has gained much attention due to its nontoxic nature, and its injection into the human body using several conjugate systems. Mainly, there are two types of CO insertion techniques into the human body, i.e., direct and indirect CO insertion. Indirect CO insertion offers an advantage of avoiding toxicity as compared to direct CO insertion. For the indirect CO inhalation method, developers are facing certain problems, such as its inability to achieve the specific cellular targets and how to control the dosage of CO. To address these issues, researchers have adopted alternative strategies regarded as CO-releasing molecules (CORMs). CO is covalently attached with metal carbonyl complexes (MCCs), which generate various CORMs such as CORM-1, CORM-2, CORM-3, ALF492, CORM-A1 and ALF186. When these molecules are inserted into the human body, CO is released from these compounds at a controlled rate under certain conditions or/and triggers. Such reactions are helpful in achieving cellular level targets with a controlled release of the CO amount. However on the other hand, CORMs also produce a metal residue (termed as i-CORMs) upon degradation that can initiate harmful toxic activity inside the body. To improve the performance of the CO precursor with the restricted development of i-CORMs, several new CORMats have been developed such as micellization, peptide, vitamins, MOFs, polymerization, nanoparticles, protein, metallodendrimer, nanosheet and nanodiamond, etc. In this review article, we shall describe modern ways of CO administration; focusing primarily on exclusive features of CORM's tissue accumulations and their toxicities. This report also elaborates on the kinetic profile of the CO gas. The comprehension of developmental phases of CORMats shall be useful for exploring the ideal CO therapeutic drugs in the future of medical sciences.
一氧化碳释放材料（CORMats）被用作产生用于治疗目的的一氧化碳分子的物质。一氧化碳（CO）在较高浓度时会对生物有机体产生毒性作用。如果以可控方式利用这一特性，它可以作为一种细胞信号分子，发挥重要的病理和药代动力学功能；从而带来许多新的应用和治疗方法。近年来，由于其无毒性质以及通过多种共轭体系将其注入人体，利用一氧化碳进行治疗应用的研究备受关注。主要有两种将一氧化碳引入人体的技术，即直接引入一氧化碳和间接引入一氧化碳。与直接引入一氧化碳相比，间接引入一氧化碳具有避免毒性的优势。对于间接一氧化碳吸入法，研发人员面临一些问题，比如无法实现特定的细胞靶向以及如何控制一氧化碳的剂量。为了解决这些问题，研究人员采用了被视为一氧化碳释放分子（CORMs）的替代策略。一氧化碳与金属羰基配合物（MCCs）共价结合，生成各种CORMs，如CORM - 1、CORM - 2、CORM - 3、ALF492、CORM - A1和ALF186。当这些分子被引入人体后，在特定条件或/和触发因素作用下，一氧化碳会以可控速率从这些化合物中释放出来。此类反应有助于在控制一氧化碳释放量的情况下实现细胞水平的靶向。然而，另一方面，CORMs在降解时也会产生金属残留物（称为i - CORMs），这些残留物可能在体内引发有害的毒性活动。为了在限制i - CORMs发展的情况下提高一氧化碳前体的性能，已经开发了几种新型的CORMats，如胶束化、肽、维生素、金属有机框架材料、聚合、纳米颗粒、蛋白质、金属树枝状大分子、纳米片和纳米金刚石等。在这篇综述文章中，我们将描述一氧化碳给药的现代方式；主要关注CORMs在组织中的蓄积特性及其毒性。本报告还详细阐述了一氧化碳气体的动力学概况。了解CORMats的发展阶段将有助于在未来医学科学中探索理想的一氧化碳治疗药物。
