Synthesis and biological evaluation of a Platinum(II)-c(RGDyK) conjugate for integrin-targeted photodynamic therapy

摘要

Abstract A cancer-targeting conjugate 4 of a cyclometalated [N,C,N-Pt(II)] complex bearing a N?C?N 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 1 O 2 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. Graphical abstract Display Omitted Highlights ? A cancer-targeting conjugate of a cyclometalated [N,C,N-Pt(II)] complex has been synthesized. ? The conjugate exhibited a mild cytostatic effect to six different cancer cell lines. ? The conjugate demonstrated rapid cell uptake by receptor-mediated endocytosis. ? The conjugate efficiently generated 1 O 2 upon irradiation. ? Conjugate 4 resulted in reduction of cell survival of AY27?cells after blue light exposure.