Photoinduced Reduction of Pt^IVwithin an Anti-Proliferative Pt^IV-Texaphyrin Conjugate

Abstract

In an effort to increase the stability and control the platinum reactivity of platinum-texaphyrin conjugates, two Pt(IV) conjugates (4 and 5, Scheme 1) were designed, synthesized, and studied for their ability to form DNA adducts. They were also tested for their anti-proliferative effects using wild-type and platinum-resistant human ovarian cancer cell lines (A2780 and 2780CP, respectively). In comparison to an analogous first generation Pt(II)-texaphyrin chimera (2, Scheme 1), conjugate 4 provided increased stability in aqueous environments. Using a combination of 1H-NMR spectroscopy and FAAS (flameless atomic-absorption spectrometry), it was found that the Pt(IV) center within conjugate 4 undergoes photo-induced reduction to Pt(II) upon exposure to glass-filtered daylight, resulting in an entity that binds DNA in a controlled manner. Under conditions where the Pt(IV) complex is reduced to the corresponding Pt(II) species, conjugates 4 and 5 demonstrated potent anti-proliferative activity in both test ovarian cancer cell lines.

Gd(iii)–Pt(iv) theranostic contrast agents for tandem MR imaging and chemotherapy

“…[15][16][17][18][19] A variety of groups can be incorporated as axial ligands to allow for tumor targeting, combination therapy, bioimaging, and controlled reduction of the Pt(IV). [20][21][22][23][24][25][26][27][28][29][30][31] Sessler and coworkers were the rst to demonstrate how Gd(III) complexes can be used synergistically with Pt(IV) prodrugs. Their Gd(III)-texaphyrin complexes have been used to increase tumor localization and mediate the reduction of Pt(IV) to Pt(II).…”

“…Their Gd(III)-texaphyrin complexes have been used to increase tumor localization and mediate the reduction of Pt(IV) to Pt(II). 30,31 However, we believe there is a signicant opportunity to investigate Gd(III)-Pt(IV) mixed metal complexes for applications as theranostic agents.…”

Activation of Platinum(IV) Prodrugs By Motexafin Gadolinium as a Redox Mediator

“…The conjugate was found to be as efficient as the original Pt(II)-TEX analogues in terms of reducing cell proliferation in vitro while being much less sensitive to hydrolysis and release of Pt(II) in the absence of photo-irradiation. [6] While attractive, the photo-irradiation approach suffers from a number of drawbacks, including poor tissue penetration by photons at the wavelengths needed for photo-activation, difficulties associated with administering light to many biological loci, and off-target light-induced toxicity effects. Here, we present a new strategy to activate Pt(IV) prodrugs that involves the use of MGd as a redox catalyst.…”

Comparison of different sample preparation methods for platinum determination in cultured cells by graphite furnace atomic absorption spectrometry

“…The combination of cisplatin and two phytochemicals (curcumin and epigallocatechin-3-gallate) could produce synergistic outcomes, i.e., greater cellular accumulation of platinum (Yunos et al, 2011). Recently, GFAAS has also been applied to investigate the newly synthesized platinum-nitroxyl complexes and platinum (IV) texaphyrin conjugate for their potential to circumvent cisplatin resistance (Cetraz et al, 2016; Thiabaud et al, 2014), which indicates that quantifying intracellular platinum concentration using the technique of GFAAS might play a role in new drug research and development.…”