Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, 61265 Brno (Czech Republic).
Regional Centre of Advanced Technologies and Materials, Department of Inorganic Chemistry, Faculty of Science, Palacky University in Olomouc, 17. listopadu 12, 77146 Olomouc (Czech Republic).
Angew Chem Int Ed Engl. 2015 Nov 23;54(48):14478-82. doi: 10.1002/anie.201506533. Epub 2015 Oct 12.
We report toxic effects of a photoactivatable platinum(IV) complex conjugated with suberoyl-bis-hydroxamic acid in tumor cells. The conjugate exerts, after photoactivation, two functions: activity as both a platinum(II) anticancer drug and histone deacetylase (HDAC) inhibitor in cancer cells. This approach relies on the use of a Pt(IV) pro-drug, acting by two independent mechanisms of biological action in a cooperative manner, which can be selectively photoactivated to a cytotoxic species in and around a tumor, thereby increasing selectivity towards cancer cells. These results suggest that this strategy is a valuable route to design new platinum agents with higher efficacy for photodynamic anticancer chemotherapy.
我们报告了一种与琥珀酰双羟肟酸偶联的光活化型铂（IV）配合物在肿瘤细胞中的毒性作用。该配合物在光活化后发挥两种功能：作为铂（II）抗癌药物和组蛋白去乙酰化酶（HDAC）抑制剂在癌细胞中的活性。这种方法依赖于使用 Pt（IV）前药，通过两种独立的生物学作用机制以协同方式起作用，可以选择性地在肿瘤内和周围光活化为细胞毒性物质，从而提高对癌细胞的选择性。这些结果表明，这种策略是设计具有更高光动力抗癌化疗疗效的新型铂剂的有价值途径。
