We report toxic effects of a photoactivatable platinum(IV) complex conjugated with suberoyl-bis-hydroxamic acid in tumor cells. The conjugate exerts, after photoactivation, two functions: activity as both a platinum(II) anticancer drug and histone deacetylase (HDAC) inhibitor in cancer cells. This approach relies on the use of a Pt(IV) pro-drug, acting by two independent mechanisms of biological action in a cooperative manner, which can be selectively photoactivated to a cytotoxic species in and around a tumor, thereby increasing selectivity towards cancer cells. These results suggest that this strategy is a valuable route to design new platinum agents with higher efficacy for photodynamic anticancer chemotherapy.
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Dalton Trans
August 2024
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
The hyphenation of HPLC with its high separation ability and ICP-MS with its excellent sensitivity, allows the analysis of Pt drugs in biological samples at the low nanomolar concentration levels. On the other hand, LC-MS provides molecular structural confirmation for each species. Using a combination of these methods, we have investigated the speciation of the photoactive anticancer complex diazido Pt(IV) complex , , -[Pt(N)(OH)(py)] (FM-190) in aqueous solution and biofluids at single-digit nanomolar concentrations before and after irradiation.
View Article and Find Full Text PDFDalton Trans
August 2023
Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44242, USA.
We hereby engineered photoactivatable Pt(IV) metallodrugs that harness CD36 to target ovarian cancer cells. Pt(IV) compounds mimic the structure of fatty acids and take advantage of CD36 as a "Trojan horse" to gain entry into the cells. We confirmed that CD36-dependent entry occurs using graphite furnace atomic absorption spectroscopy with ovarian cancer cells expressing different levels of CD36 and a CD36 inhibitor, SSO.
View Article and Find Full Text PDFFront Chem
June 2022
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
Photoactivatable Pt(IV) anticancer prodrugs with the structure of [Pt(N)(N)(L)(L)(A)(A)], where N and N are non-leaving nitrogen donor ligands, L and L are leaving ligands, and A and A are axial ligands, have attracted increasing attention due to their promising photo-cytotoxicity even to cisplatin-resistant cancer cells. These photochemotherapeutic prodrugs have high dark-stability under physiological conditions, while they can be activated by visible light restrained at the disease areas, as a consequence showing higher spatial and temporal controllability and much more safety than conventional chemotherapy. The coordinated ligands to the Pt center have been proved to be pivotal in determining the function and activity of the photoactivatable Pt(IV) prodrugs.
View Article and Find Full Text PDFInorg Chem Front
September 2020
Czech Academy of Sciences, Institute of Biophysics, Kralovopolska 135, CZ-61265 Brno, Czech Republic.
The platinum() prodrug trans,trans,trans-[Pt(N)(OH)(py)] (1) is stable and non-toxic in the dark, but potently cytotoxic to cancer cells when irradiated by visible light, including cisplatin-resistant cells. On irradiation with visible light, it generates reactive Pt(II) species which can attack DNA, and produces reactive oxygen species (ROS) and reactive nitrogen species (RNS) which exert unusual effects on biochemical pathways. We now show that its novel mechanism of action includes induction of immunogenic cell death (ICD).
View Article and Find Full Text PDFAdv Healthc Mater
October 2021
Faculty of Chemistry, Northeast Normal University, Changchun, 130024, P.R. China.
Stimuli-responsive nanosystems have been widely applied as effective modalities for drug/gene co-delivery in cancer treatment. However, precise spatiotemporal manipulations of drug/gene co-delivery, as well as multi-modality imaging-guided cancer therapy, still remain a daunting challenge. Here, multifunctional polyprodrug/siRNA loaded upconversion nanoparticles (UCNPs) are reported that combine computed tomography (CT), magnetic resonance (MR), and upconversion luminescence (UCL) tri-modality imaging and near-infrared (NIR) light-activated drug/gene on-demand delivery.
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