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

被引：46

作者：

Chatzisideri, T. ^{[1
]}

Thysiadis, S. ^{[1
]}

Katsamakas, S. ^{[2
]}

Dalezis, P. ^{[3
]}

Sigala, I. ^{[1
]}

Lazarides, T. ^{[1
]}

Nikolakaki, E. ^{[1
]}

Trafalis, D. ^{[3
]}

Gederaas, O. A. ^{[4
]}

Lindgren, M. ^{[5
]}

Sarli, V. ^{[1
]}

机构：

[1] Aristotle Univ Thessaloniki, Dept Chem, Univ Campus, Thessaloniki 54124, Greece

[2] Aristotle Univ Thessaloniki, Sch Pharm, Dept Pharmaceut Chem, Univ Campus, Thessaloniki 54124, Greece

[3] Natl & Kapodistrian Univ Athens, Med Sch, Lab Pharmacol, 75 Mikras Asias St, Athens 11527, Greece

[4] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, NTNU, N-7491 Trondheim, Norway

[5] Norwegian Univ Sci & Technol, Dept Phys, NTNU, N-7491 Trondheim, Norway

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 141卷

关键词：

Targeted drug delivery; RGD peptide; Integrin av beta 3; Angiogenesis; Tumor therapy; Pt(II)-RGD conjugate; Photodynamic therapy; Theranostic agent; CYCLOMETALATED PT(II) COMPLEXES; METAL-COMPLEXES; IN-VITRO; PHOTOPHYSICAL PROPERTIES; CANCER-THERAPY; BREAST-CANCER; DELIVERY; EXPRESSION; EMISSION; LUMINESCENCE;

D O I：

10.1016/j.ejmech.2017.09.058

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A cancer-targeting conjugate 4 of a cyclometalated [N,C,N-Pt(II)] complex bearing a (NCN)-C-boolean AND-N-boolean AND 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-1(2) upon irradiation. Incubation of rat bladder cancer cells AY27 with conjugate 4 (50 mu M) prior to blue light exposure (5 min) resulted in significant reduction (50%) of cell survival compared to control cells as measured by MIT assay post 24 h after treatment. (C) 2017 Elsevier Masson SAS. All rights reserved.

引用

页码：221 / 231

页数：11

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