Ahmedova Anife, Mihaylova Rositsa, Momekova Denitsa, Shestakova Pavletta, Stoykova Silviya, Zaharieva Joana, Yamashina Masahiro, Momekov Georgi, Akita Munetaka, Yoshizawa Michito
Faculty of Chemistry and Pharmacy, University of Sofia, 1, J. Bourchier blvd., Sofia 1164, Bulgaria.
Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, Sofia 1000, Bulgaria.
Dalton Trans. 2016 Aug 16;45(33):13214-21. doi: 10.1039/c6dt01801g.
Metallosupramolecular cages and capsules have gained increasing popularity as both molecular containers and anticancer agents. For successful combination of these properties a thorough analysis of the effect of guest encapsulation on the host's cytotoxic properties is highly required. Here we report on the cytotoxicity modulation of Pt(ii) and Pd(ii)-linked M2L4 coordination capsules upon encapsulation of guest molecules such as pyrene and caffeine. The anticancer activity of the capsules against various human cancer cells (HT-29, T-24, HL-60 and its resistant counterparts HL-60/Dox and HL-60/CDDP) significantly altered upon the guest encapsulation. The encapsulation of pyrene molecules causes a decrease in the cytotoxicity of the Pt(ii) capsule, which is stronger than that of the Pd(ii) capsule. The cytotoxicities of the caffeine containing capsules are lower than that of the empty capsules (except for HL-60), but still superior to cisplatin under the same conditions. The observed trends in the anticancer activity of the capsules and their host-guest complexes correlate with their different stabilities toward glutathione, estimated by NMR-based kinetic experiments. Mechanistic insights into the observed cytotoxicities are obtained by fluorescence microscopy imaging of tumor cells treated with the capsules and their pyrene complexes. The data suggest the glutathione-triggered disassembly of the capsular structures as a potential activation pathway for their cytotoxicities.
金属超分子笼和胶囊作为分子容器和抗癌剂越来越受到关注。为了成功结合这些特性，非常需要深入分析客体包封对主体细胞毒性特性的影响。在此，我们报道了客体分子芘和咖啡因包封后，Pt(ii)和Pd(ii)连接的M2L4配位胶囊的细胞毒性调节情况。客体包封后，胶囊对各种人类癌细胞（HT-29、T-24、HL-60及其耐药对应物HL-60/Dox和HL-60/CDDP）的抗癌活性发生了显著变化。芘分子的包封导致Pt(ii)胶囊的细胞毒性降低，且这种降低比Pd(ii)胶囊更明显。含咖啡因的胶囊的细胞毒性低于空胶囊（HL-60除外），但在相同条件下仍优于顺铂。通过基于核磁共振的动力学实验估计，观察到的胶囊及其主客体配合物的抗癌活性趋势与其对谷胱甘肽的不同稳定性相关。通过对用胶囊及其芘配合物处理的肿瘤细胞进行荧光显微镜成像，获得了对观察到的细胞毒性的机理见解。数据表明，谷胱甘肽触发的胶囊结构解体是其细胞毒性的潜在激活途径。
