Fighting Cancer with Corroles.
Fighting Cancer with Corroles.
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DOI：
10.1021/acs.chemrev.6b00400
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发表时间：
2017-02-22
期刊：
影响因子：
62.1
通讯作者：
Gray HB
中科院分区：
文献类型：
--
作者：
Teo RD;Hwang JY;Termini J;Gross Z;Gray HB
Corroles是开发同时用于癌症靶向成像和治疗的药物的非常有前途的平台。根据被咔咯螯合的元素，这些治疗诊断剂可以主要针对诊断或治疗功能进行调整。通用的合成方法允许制备双极性衍生物，其与靶向生物分子形成稳定的非共价缀合物。这些缀合物可以被工程化用于在一个治疗诊断组件内成像、靶向以及治疗功能。在这篇综述中，我们开始与一个简单的概述了可咯化学，已独特的有用的设计腐蚀为基础的抗癌药物。然后，我们将注意力转向关于咔咯抗癌活性的早期文献，该文献在第一个可扩展的合成报告后一年开始（1999-2000）。在2001年，一个主要的进展是引入了带负电荷的corroles，因为这些分子是双极性的，与许多蛋白质形成稳定的缀合物。最近，在采用先进的光学光谱以及磁共振成像技术的实验研究中，已经记录了metalcorroles的细胞摄取和细胞内运输。从细胞和动物模型的工作的关键结果进行审查，重点是那些揭示了新的光与抗癌活性的机制。最后，我们预测了一个非常光明的未来corrole抗癌研究，因为它正在经历指数增长，充分利用最近开发的成像和治疗方式。
Corroles are exceptionally promising platforms for the development of agents for simultaneous cancer-targeting imaging and therapy. Depending on the element chelated by the corrole, these theranostic agents may be tuned primarily for diagnostic or therapeutic function. Versatile synthetic methodologies allow for the preparation of amphipolar derivatives, which form stable noncovalent conjugates with targeting biomolecules. These conjugates can be engineered for imaging, targeting, as well as therapeutic function within one theranostic assembly. In this review, we begin with a brief outline of corrole chemistry that has been uniquely useful in designing corrole-based anticancer agents. Then we turn attention to the early literature regarding corrole anticancer activity, which commenced one year after the first scalable synthesis was reported (1999–2000). In 2001, a major advance was made with the introduction of negatively charged corroles, as these molecules, being amphipolar, form stable conjugates with many proteins. More recently, both cellular uptake and intracellular trafficking of metallocorroles have been documented in experimental investigations employing advanced optical spectroscopic as well as magnetic resonance imaging techniques. Key results from work on both cellular and animal models are reviewed, with emphasis on those that have shed new light on the mechanisms associated with anticancer activity. In closing, we predict a very bright future for corrole anticancer research, as it is experiencing exponential growth, taking full advantage of recently developed imaging and therapeutic modalities.
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