Application of a Novel Metallomics Tool to Probe the Fate of Metal-Based Anticancer Drugs in Blood Plasma: potential, challenges and prospects

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dc.contributor.authorSarpong-Kumankomah, Sophia
dc.contributor.authorGailer, Juergen
dc.date.accessioned2021-09-13T15:45:17Z
dc.date.available2021-09-13T15:45:17Z
dc.date.issued2020-06-27
dc.description.abstractAlthough 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.en_US
dc.identifier.citationSarpong-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.en_US
dc.identifier.doi10.2174/1568026620666200628023540en_US
dc.identifier.urihttp://hdl.handle.net/1880/113855
dc.identifier.urihttps://dx.doi.org/10.11575/PRISM/39183
dc.language.isoengen_US
dc.publisherBenthamen_US
dc.publisher.departmentChemistryen_US
dc.publisher.facultyScienceen_US
dc.publisher.hasversionacceptedVersionen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.publisher.policyhttps://benthamscience.com/self-archiving-policies-main.phpen_US
dc.rightsUnless otherwise indicated, this material is protected by copyright and has been made available with authorization from the copyright owner. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectmetal-based drugsen_US
dc.subjectcombination therapyen_US
dc.subjectbimetallic complexesen_US
dc.subjectbiotransformationen_US
dc.subjectsafetyen_US
dc.subjectside-effectsen_US
dc.subjectmetallomicsen_US
dc.subjectdrug developmenten_US
dc.titleApplication of a Novel Metallomics Tool to Probe the Fate of Metal-Based Anticancer Drugs in Blood Plasma: potential, challenges and prospectsen_US
dc.typejournal articleen_US
ucalgary.item.requestcopytrueen_US
ucalgary.scholar.levelFacultyen_US
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