Photoactivatable metal complexes offer the prospect of novel drugs with low side effects and new mechanisms of action to combat resistance to current therapy. We highlight recent progress in the design of platinum, ruthenium, iridium, gold and other transition metal complexes, especially for applications as anticancer and anti-infective agents. In particular, understanding excited state chemistry related to identification of the bioactive species (excited state metallomics/pharmacophores) is important. Photoactivatable metallodrugs are classified here as photocatalysts, photorelease agents and ligand-activated agents. Their activation wavelengths, cellular mechanisms of action, experimental and theoretical metallomics of excited states and photoproducts are discussed to explore new strategies for the design and investigation of photoactivatable metallodrugs. These photoactivatable metallodrugs have potential in clinical applications of Photodynamic Therapy (PDT), Photoactivated Chemotherapy (PACT) and Photothermal Therapy (PTT).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/anie.202423335 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Advances in the Design of Photoactivatable Metallodrugs: Excited State Metallomics.
Angew Chem Int Ed Engl
January 2025
Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.
Photoactivatable metal complexes offer the prospect of novel drugs with low side effects and new mechanisms of action to combat resistance to current therapy. We highlight recent progress in the design of platinum, ruthenium, iridium, gold and other transition metal complexes, especially for applications as anticancer and anti-infective agents. In particular, understanding excited state chemistry related to identification of the bioactive species (excited state metallomics/pharmacophores) is important.
View Article and Find Full Text PDFNear-Infrared-II-Activated Transition Metal(II)-Coordinated Ligand Radical Primes Robust Anticancer Immunity.
J Med Chem
December 2024
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Key Laboratory of Functional Polymer Materials of Ministry of Education, Nankai University, Tianjin 300071, China.
Photoactivatable metallodrugs combining tumor cell eradication and immune stimulation hold immense promise for targeted cancer therapy. However, limitations such as oxygen dependence, narrow visible light responsiveness, and poor immunogenicity hinder their efficacy in deep solid tumors with hypoxic and immunosuppressive microenvironments. Herein, we present a novel design strategy for transition metal(II)-coordinated ligand radicals exhibiting intense near-infrared-II (NIR-II) absorption, unique endoplasmic reticulum-targeting capability, and oxygen-independent photothermal performance, effectively addressing these constraints.
View Article and Find Full Text PDFVisible light-activatable platinum(IV) prodrugs harnessing CD36 for ovarian cancer therapy.
Dalton 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 PDFDifferentiated oxidation modes of guanine between CpG and CpG by a photoactivatable Pt(IV) anticancer prodrug.
Dalton Trans
February 2023
Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials; School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P. R. China.
CpG and its cytosine-methylated counterpart (CpG) are a unique reversible pair of sequences in regulating the expression of genes epigenetically. As DNA is the potential target of Pt-based anticancer metallodrugs, herein, we comparatively investigate the interactions of 5'-CpG and 5'-CpG with a photoactivatable anticancer Pt(IV) prodrug, ,,-[Pt(N)(OH)(py)] (1; py = pyridine), to explore the effects of methylation on the platination and ROS-induced oxidation of the CpG motif. Mono-platinated dinucleotides were demonstrated by ESI-MS to be the main products for both 5'-CpG and 5'-CpG with the bound Pt moiety as [Pt(N)(py)] generated by the photodecomposition of complex 1 under irradiation with blue light, accompanied by the formation of less abundant di-platinated adducts.
View Article and Find Full Text PDFModulation of Amyloidogenic Peptide Aggregation by Photoactivatable CO-Releasing Ruthenium(II) Complexes.
Pharmaceuticals (Basel)
July 2020
Department of Pharmacy, University of Naples Federico II, 80134 Napoli, Italy.
Three Ru(II)-based CO-releasing molecules featuring bidentate benzimidazole and terpyridine derivatives as ligands were investigated for their ability to modulate the aggregation process of the second helix of the C-terminal domain of nucleophosmin 1, namely nucleophosmin 1 (NPM1), a model amyloidogenic system, before and after irradiation at 365 nm. Thioflavin T (ThT) binding assays and UV/Vis absorption spectra indicate that binding of the compounds to the peptide inhibits its aggregation and that the inhibitory effect increases upon irradiation (half maximal effective concentration (EC) values in the high micromolar range). Electrospray ionization mass spectrometry data of the peptide in the presence of one of these compounds confirm that the modulation of amyloid aggregation relies on the formation of adducts obtained when the Ru compounds react with the peptide upon releasing of labile ligands, like chloride and carbon monoxide.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!