Τίτλος:
Synthesis and biological evaluation of a Platinum(II)-c(RGDyK) conjugate for integrin-targeted photodynamic therapy
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 1O2 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. © 2017 Elsevier Masson SAS
Συγγραφείς:
Chatzisideri, T.
Thysiadis, S.
Katsamakas, S.
Dalezis, P.
Sigala, I.
Lazarides, T.
Nikolakaki, E.
Trafalis, D.
Gederaas, O.A.
Lindgren, M.
Sarli, V.
Περιοδικό:
European Journal of Medicinal Chemistry
Εκδότης:
Elsevier Masson SAS
Λέξεις-κλειδιά:
4 (2,5 dioxopyrrolidin 1 yl)carbonyl 2,6 bis(pyridin 2 yl)phenyl]platinum(II) chloride; 4 carboxy 2,6 bis(pyridin 2 yl)phenyl]platinum(II) chloride; amino acid; arginylglycylaspartic acid; cytostatic agent; dimethyl sulfoxide; integrin; methyl 3,5 bis(4,4,5,5 tetramethyl 1,3,2 dioxaborolan 2 yl)benzoate; methyl 3,5 di(pyridin 2 yl)benzoate; okadaic acid; platinum complex; singlet oxygen; unclassified drug; water; [4 (methoxycarbonyl) 2,6 bis(pyridin 2 yl)phenyl]platinum(II) chloride; antineoplastic agent; arginyl-glycyl-aspartic acid; integrin; oligopeptide; platinum; platinum complex, A-549 cell line; animal cell; antiproliferative activity; Article; astrocytoma cell line; AY-27 cell line; blue light; cancer inhibition; cell survival; cell viability; confocal microscopy; controlled study; drug conjugation; drug cytotoxicity; drug delivery system; drug design; drug stability; drug synthesis; drug targeting; drug uptake; electrospray mass spectrometry; endocytosis; female; fluorescence analysis; HeLa cell line; high performance liquid chromatography; human; human cell; IC50; in vitro study; irradiation; light exposure; liquid chromatography-mass spectrometry; luminescence; MCF-7 cell line; MDA-MB-231 cell line; microwave irradiation; MTT assay; nonhuman; PC-3 [Human prostate carcinoma] cell line; photodynamic therapy; protein expression; proton nuclear magnetic resonance; rat; SK-OV-3 cell line; U87M cell line; ultraviolet radiation; animal; antagonists and inhibitors; cell proliferation; chemical structure; chemistry; dose response; drug effects; drug screening; metabolism; photochemotherapy; structure activity relation; synthesis; tumor cell line, Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Integrins; Molecular Structure; Oligopeptides; Organoplatinum Compounds; Photochemotherapy; Platinum; Rats; Structure-Activity Relationship
DOI:
10.1016/j.ejmech.2017.09.058
