Application of a Novel Metallomics Tool to Probe the Fate of Metal-Based Anticancer Drugs in Blood Plasma: potential, challenges and prospects
Date
2020-06-27
Journal Title
Journal ISSN
Volume Title
Publisher
Bentham
Abstract
Although metallodrugs are in use to treat a variety of human disorders and exhibit a remarkable diversity of therapeutic properties, they constitute only a tiny minority of all medicinal drugs that are currently on the market. This undesirable situation must be partially attributed to our general lack of understanding the fate of metallodrugs in the extremely ligand-rich environment of the bloodstream. The challenge of gaining insight into these bioinorganic processes can be overcome by the application of ‘metallomics tools’, which involve the analysis of a biological fluid (e.g. blood plasma) with a separation method in conjunction with multi-element specific detectors. To this end, we have developed a metallomics tool that is based on size-exclusion chromatography (SEC) hyphenated to an inductively coupled plasma atomic emission spectrometer (ICP-AES). After the successful application of SEC-ICP-AES to analyze plasma for endogenous copper, iron and zinc-metalloproteins, it was subsequently applied to probe the metabolism of a variety of metal-based anticancer drugs in plasma. The versatility of this metallomics tool is exemplified by the fact that it has provided insight into the metabolism of individual Pt-based drugs, the modulation of the metabolism of cisplatin by sulfur-containing compounds, the metabolism of two metal-based drugs that contain different metals as well as a bimetallic anticancer drug, which contained two different metals. After adding pharmacologically relevant doses of metallodrugs to plasma, the temporal analysis of aliquots by SEC-ICP-AES allows to observe metal-protein adducts, metallodrug-derived degradation products and the parent metallodrug(s). This unique capability allows to obtain comprehensive insight into the fate of metal-based drugs in plasma and can be extended to in vivo studies. Thus, the application of this metallomics tool to probe the fate of novel metal-complexes in plasma that exert the desired biological activity has the potential to advance more metal-based drugs to animal/preclinical studies to fully explore the potential that metallodrugs inherently offer.
Description
Keywords
metal-based drugs, combination therapy, bimetallic complexes, biotransformation, safety, side-effects, metallomics, drug development
Citation
Sarpong-Kumankomah, S., & Gailer, J. (2021). Application of a novel metallomics tool to probe the fate of metal-based anticancer drugs in blood plasma: Potential, challenges and prospects. Current Topics in Medicinal Chemistry, 21(1), 48-58.