Functionalization of Ruthenium(II) Terpyridine Complexes with Cyclic RGD Peptides To Target Integrin Receptors in Cancer Cells

Abstract

Abstract:The lack of selectivity for cancer cells and the resulting negative impact on healthy tissue is a severe drawback of actual cancer chemotherapy. Tethering of cytotoxic drugs to targeting vectors such as peptides, which recognize receptors overexpressed on the surface of tumor cells, is one possible strategy to overcome such a problem. The pentapeptide cyc(RGDfK) targets the integrin receptor α v 3 , important for tumor growth and metastasis formation. In this work, two terpyridine-based Ru II complexes were prepared and for the first time conjugated to cyc(RGDfK) through amide bond formation, which resulted in a monomeric and a dimeric bioconjugate.

Photophysics and Cell Uptake of Self-Assembled Ru(II)Polypyridyl Vesicles

“…These include modifying compound charge and hydrophilicity or conjugation of biological moieties to the probe (Zhang and Lo, 2009 ; Pisani et al, 2010 ; Li et al, 2013 ; Lo, 2015 ; Zabarska et al, 2016 ; Caporale et al, 2017 ; Chakrabortty et al, 2017 ; Dolan et al, 2017 ; Caporale and Massi, 2018 ). Our work has focused on the use of bioconjugation, especially of cell penetrating (CPP) and signal peptides and we have shown, that this can be a highly effective means of targeting (Dolan et al, 2017 ; Hahn et al, 2017 ) However, the associated synthesis and purification is expensive and time consuming.…”

Toward Angiogenesis Inhibitors Based on the Conjugation of Organometallic Platinum(II) Complexes to RGD Peptides

“…First, it is worth noting that the cytotoxic activity of the parent Pt complex (2)w as lower in all cell lines tested (Table 1a nd Figure3)c ompared with A2780 cells, which were previously found to be highly sensitive to this compound (IC 50 = 0.98 mm). [32][33][34][35][36] Furthermore, it was found that 1 was not cytotoxic in any of the cell lines tested. This result was not completely unexpected upon taking into account the low cytotoxic activity of 2 in a V b 3 /a V b 5 + cells, and the fact that conjugation was usually accompanied by ar eduction of the antitumor activity of the free metallodrug.…”

“…This result was not completely unexpected upon taking into account the low cytotoxic activity of 2 in a V b 3 /a V b 5 + cells, and the fact that conjugation was usually accompanied by ar eduction of the antitumor activity of the free metallodrug. [32][33][34][35][36] Furthermore, it was found that 1 was not cytotoxic in any of the cell lines tested. Interestingly,w eo bserved am arked effect of 3 on the morphologyo fa V b 3 -overexpressing SK-MEL-28 cells and a V b 5 -overexpressing MDA-MB-231 cells.…”

Strategies to promote permeation and vectorization, and reduce cytotoxicity of metal complex luminophores for bioimaging and intracellular sensing

“…This may be because the complex is bound by integrin at the cell surface rather than permeating to the cytoplasm, but such an approach is nonetheless potentially very useful in cancer imaging. 177 Fernández-Moreira et al have contributed recent work in this field, synthesising the peptide linked heterobimetallic Ir(III)/Au(I) complexes 50 and 51 (Fig. 29).…”