Chatzisideri T, Thysiadis S, Katsamakas S, Dalezis P, Sigala I, Lazarides T, Nikolakaki E, Trafalis D, Gederaas O A, Lindgren M, Sarli V
Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124, Thessaloniki, Greece.
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, University Campus, 54124, Thessaloniki, Greece.
Eur J Med Chem. 2017 Dec 1;141:221-231. doi: 10.1016/j.ejmech.2017.09.058. Epub 2017 Sep 28.
A cancer-targeting conjugate 4 of a cyclometalated [N,C,N-Pt(II)] complex bearing a NˆCˆN 1,3-di(2-pyridyl)-benzene with c(RGDyK) peptide as guiding molecule was designed and synthesized for real-time drug delivery monitoring in cancer cells and photodynamic therapy (PDT). This conjugate demonstrates a mild cytostatic effect to six cancer cell lines expressing integrins at different extent, while possessing promising features for PDT. Conjugate 4 demonstrated rapid cell uptake by receptor-mediated endocytosis and efficient generation of O upon irradiation. Incubation of rat bladder cancer cells AY27 with conjugate 4 (50 μΜ) prior to blue light exposure (5 min) resulted in significant reduction (50%) of cell survival compared to control cells as measured by MTT assay post 24 h after treatment.
设计并合成了一种以环金属化的[N,C,N-Pt(II)]配合物为基础的癌症靶向共轭物4，该配合物带有NˆCˆN 1,3-二(2-吡啶基)-苯，并以c(RGDyK)肽作为导向分子，用于癌细胞中的实时药物递送监测和光动力疗法(PDT)。该共轭物对六种不同程度表达整合素的癌细胞系表现出温和的细胞生长抑制作用，同时具有光动力疗法的良好特性。共轭物4通过受体介导的内吞作用表现出快速的细胞摄取，并在照射后有效产生活性氧。在用共轭物4(50μM)孵育大鼠膀胱癌细胞AY27后进行蓝光照射(5分钟)，与对照细胞相比，在处理后24小时通过MTT测定法测量，细胞存活率显著降低(50%)。
