Abstract
Nanofocused synchrotron X-ray fluorescence and inductively coupled plasma-mass spectrometry provide insights into time-dependent ligand exchange reactions of organo-osmium anticancer complexes in cancer cells. Created with Biorender.com.
Highlights
We use a combination of synchrotron nanoprobe X-ray fluorescence (XRF) from Os L3M5 and Br KL3 emissions and inductively coupled plasmamass spectrometry (ICP-MS) detection of 189Os, 79Br, and 127I, to investigate the time-dependent accumulation and localization of osmium as well as the monodentate ligand and the chelated phenylazopyridine in A2780 human ovarian cancer cells treated with the potent anticancer complexes [Os(η6-pcymene)(4-R2-phenyl-azopyridine-5-R1)X]PF6, with R2 = NMe2 or OH, R1 = H or Br, and X = Cl or I
Such drug candidates include inert prodrugs that are activated through metal reduction (i.e. Pt(IV) or Ru(III) complexes), to redox-active complexes that modulate the redox balance in cancer cells producing reactive oxygen species (ROS), or altering the level of key cellular cofactors
We used nano-focused XRF to probe the effect of different halogen ligands on the time-dependent accumulation and localisation of half-sandwich Os(II) azopyridine complexes in cancer cells
Summary
Metal complexes capable of undergoing intracellular redox reactions are promising alternative anticancer treatments to Pt(II) agents, which bind to DNA and are currently used in the clinic.[1,2,3,4,5,6,7,8,9,10,11,12] Such drug candidates include inert prodrugs that are activated through metal reduction (i.e. Pt(IV) or Ru(III) complexes), to redox-active complexes that modulate the redox balance in cancer cells producing reactive oxygen species (ROS), or altering the level of key cellular cofactors.Recently, we have reported promising Os(II) arene and Ir(III) cyclopentadienyl half-sandwich anticancer complexes containing azopyridine ligands, which are activated in cancer cells and modulate their metabolism through redox processes. We used nano-focused XRF to probe the effect of different halogen ligands on the time-dependent accumulation and localisation of half-sandwich Os(II) azopyridine complexes in cancer cells.
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