| Title: |
A trackable trinuclear platinum complex for breast cancer treatment |
| Authors: |
O’Carroll, Sinéad; Slator, Creina; de Paiva, Raphael E F; Newsome, Conor; Searle, Bethany; KK, Sriram; Whittle, Sylvia; Catley, Thomas E; Scoditti, Stefano; Mnich, Katarzyna; Peterson, Erica J; Hu, Bin; Koblinski, Jennifer E; Samali, Afshin; McKee, Vickie; Pyne, Alice L B; Westerlund, Fredrik; Farrell, Nicholas P; Kellett, Andrew |
| Contributors: |
Science Foundation Ireland; Irish Research Council; Novo Nordisk Foundation; European Union’s Horizon 2020; Government of Ireland Postdoctoral Fellowship; UKRI Future Leaders Fellowship; EPSRC; European Research Council; Swedish Research Council; Swedish Cancer Foundation; Swedish Child Cancer Foundation; European Union – NextGenerationEU – PNRR; Juan de la Cierva; Ministry of Science, Innovation and Universities; European Social Fund Plus; Virginia Commonwealth University Cancer Mouse Models Core Laboratory; Tissue and Data Acquisition and Analysis Core Laboratory; Massey Cancer Center from NIH-NCI Cancer Center |
| Source: |
Nucleic Acids Research ; volume 53, issue 13 ; ISSN 0305-1048 1362-4962 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2025 |
| Description: |
Cancer remains a leading cause of death, with triple-negative breast cancer (TNBC) being particularly significant due to limited treatment options. As such, there is interest in anticancer polynuclear platinum(II) complexes, attributed to their unique DNA-binding modes and potential against therapy-resistant cancer phenotypes. However, a persistent challenge with polynuclear compounds is their lack of cellular trackability, hindering their effectiveness and monitoring in clinical settings. Here, we report the preparation of a new azide-appended trinuclear platinum complex, N3-TriplatinNC, and characterize its DNA-targeting, cytotoxicity, and topoisomerase relaxation properties from the nanoscale to the macroscale. Using single-molecule biophysics and in-liquid atomic force microscopy, N3-TriplatinNC was identified as a powerful DNA recognition agent with remarkable potential towards the TNBC cell line, MDA-MB-231. Installation of the azide handle on the polynuclear complex was achieved using a first-in-class approach to produce a complex that retained analogous biological activity to the parent TriplatinNC. Importantly, the azide handle facilitates in situ click chemistry for tracking cellular localization, with subsequent xenograft studies demonstrating in vivo antitumoural potential. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/nar/gkaf628 |
| Availability: |
https://doi.org/10.1093/nar/gkaf628; https://academic.oup.com/nar/article-pdf/53/13/gkaf628/63778856/gkaf628.pdf |
| Rights: |
https://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.4A106948 |
| Database: |
BASE |