Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
The Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
Drug Resist Updat. 2023 Mar;67:100931. doi: 10.1016/j.drup.2023.100931. Epub 2023 Jan 21.
Corroles provide a remarkable opportunity for the development of cancer theranostic agents among other porphyrinoids. While most transition metal corrole complexes are only therapeutic, post-transition metallocorroles also find their applications in bioimaging. Moreover, corroles exhibit excellent photo-physicochemical properties, which can be harnessed for antitumor and antimicrobial interventions. Nevertheless, these intriguing, yet distinct properties of corroles, have not attained sufficient momentum in cancer research. The current review provides a comprehensive summary of various cancer-relevant features of corroles ranging from their structural and photophysical properties, chelation, protein/corrole interactions, to DNA intercalation. Another aspect of the paper deals with the studies of corroles conducted in vitro and in vivo with an emphasis on medical imaging (optical and magnetic resonance), photo/sonodynamic therapies, and photodynamic inactivation. Special attention is also given to a most recent finding that shows the development of pH-responsive phosphorus corrole as a potent antitumor drug for organelle selective antitumor cytotoxicity in preclinical studies. Another biomedical application of corroles is also highlighted, signifying the application of water-soluble and completely lipophilic corroles in the photodynamic inactivation of microorganisms. We strongly believe that future studies will offer a greater possibility of utilizing advanced corroles for selective tumor targeting and antitumor cytotoxicity. In the line with future developments, an ideal pipeline is envisioned on grounds of cancer targeting nanoparticle systems upon decoration with tumor-specific ligands. Hence, we envision that a bright future lies ahead of corrole anticancer research and therapeutics.
金属卟啉类化合物中，金属叶啉提供了一个开发癌症治疗诊断试剂的绝佳机会。虽然大多数过渡金属金属叶啉配合物仅具有治疗作用，但后过渡金属金属叶啉配合物也在生物成像中有其应用。此外，金属叶啉还表现出优异的光物理化学性质，可用于抗肿瘤和抗菌干预。然而，这些引人入胜但又截然不同的金属叶啉特性，在癌症研究中还没有得到足够的重视。本综述全面总结了金属叶啉在癌症相关方面的各种特性，包括其结构和光物理性质、螯合作用、蛋白质/金属叶啉相互作用、DNA 插入等。本文的另一个方面涉及在体外和体内进行的金属叶啉研究，重点是医学成像（光学和磁共振）、光/声动力学治疗和光动力失活。特别关注的是最近的一项发现，表明开发 pH 响应性磷金属叶啉作为一种有效的抗肿瘤药物，用于临床前研究中的细胞器选择性抗肿瘤细胞毒性。还强调了金属叶啉的另一个生物医学应用，表明水溶性和完全亲脂性金属叶啉在微生物光动力失活中的应用。我们坚信，未来的研究将为利用先进的金属叶啉进行选择性肿瘤靶向和抗肿瘤细胞毒性提供更大的可能性。根据未来的发展，我们设想了一个理想的方案，即在肿瘤特异性配体修饰的基础上，构建用于癌症靶向的纳米粒子系统。因此，我们预计金属叶啉的抗癌研究和治疗前景一片光明。
