Mitra Koushambi
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560-012, India.
Dalton Trans. 2016 Dec 6;45(48):19157-19171. doi: 10.1039/c6dt03665a.
Site-specific delivery and amenable activation of prodrugs are indispensible criteria for designing novel anticancer agents. Platinum based drugs vanguard the chemotherapeutic regimes and over the years significant attention has been paid to achieve more efficacious drugs with fewer adverse effects. The switch from platinum(ii) drugs to the inert platinum(iv) analogues proved advantageous but the new prodrugs still suffered from unspecific cytotoxic actions. Thus the photoactivation of an inert platinum prodrug specifically within neoplastic cells provided the desired spatio-temporal control over drug activation by means of illumination, thereby limiting the cytotoxic events to only at the targeted tumors. This article collates research on platinum complexes which exhibit potential light mediated anticancer effects and provides insights into the underlying mechanisms of activation. Fine tuning of the coordination sphere results in dramatic alteration of the redox and spectral properties of both ground and excited states and the cellular properties of the molecules. This concise article highlights the various light promoted strategies employed to attain a controlled release of active platinum(ii) and/or reactive oxygen species such as photoreduction, photocaging, photodissociation and photosensitization. Such dual action photoactive metal complexes with improved aqueous solubility and versatility are promising candidates for combination therapy which is likely to be the future of anticancer research.
前体药物的位点特异性递送和可控激活是设计新型抗癌药物不可或缺的标准。铂类药物在化疗方案中处于前沿地位,多年来人们一直致力于研发疗效更高、副作用更小的药物。从铂(II)药物转向惰性铂(IV)类似物已被证明具有优势,但新的前体药物仍存在非特异性细胞毒性作用。因此,惰性铂前体药物在肿瘤细胞内的光激活通过光照实现了对药物激活所需的时空控制,从而将细胞毒性作用限制在仅靶向肿瘤部位。本文整理了关于具有潜在光介导抗癌作用的铂配合物的研究,并深入探讨了其激活的潜在机制。配位环境的微调会导致基态和激发态的氧化还原和光谱性质以及分子的细胞性质发生显著变化。这篇简明文章重点介绍了为实现活性铂(II)和/或活性氧的可控释放而采用的各种光促进策略,如光还原、光笼合、光解离和光敏化。这种具有改善的水溶性和多功能性的双作用光活性金属配合物有望成为联合治疗的候选药物,联合治疗可能是抗癌研究的未来方向。