Triple-Negative Breast Cancer Versus Non-Triple-Negative Breast Cancer - The Impact of Pd and Pt Complexes on Basal-Like Triple-Negative Breast Cancer

Sep 22, 2026

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Breast cancer remains a major cause of morbidity and mortality, while triple-negative breast cancer (TNBC) is highly aggressive with frequent metastasis. This research evaluates complexes containing two or three metal centres linked to biogenic polyamines—putrescine (Pd2Put2 and Pt2Put2(NH3)4) and spermidine (Pd3Spd2 and Pt3Spd2)—along with cisplatin against non-malignant MCF-12A, TNBC MDA-MB-468 and non-TNBC MCF-7 cell lines. Cell viability and micro-FTIR/micro-Raman analyses show TNBC-selective activity, including stronger Pd3Spd2 DNA effects and Pt2Put2(NH3)4 protein modulation, supporting rational anticancer drug design with improved efficiency and reduced toxicity.

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Abstract

Introduction

ChemMedChem RESEARCH ARTICLE Triple-Negative Breast Cancer Versus Non-Triple-Negative Breast Cancer: The Impact of Pd and Pt Complexes on Basal-Like Triple-Negative Breast Cancer Clara B. Martins1,2 | Maria P. M. Marques1,2 | Luís A. E. Batista de Carvalho1 | Ana L. M. Batista de Carvalho1 1Molecular Physical-Chemistry, LAQV/REQUIMTE, Department of Chemistry, University of Coimbra, Coimbra, Portugal | 2Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal Correspondence: Ana L. M. Batista de Carvalho ([almbc@uc.pt](almbc@uc.pt)) Received: 22 September 2025 | Revised: 23 April 2026 | Accepted: 24 April 2026 Keywords: anticancer activity | micro-FTIR | micro-Raman | polynuclear complexes | triple-negative breast cancer ABSTRACT Breast cancer (BC) is the most common cancer in women, with a high mortality. Triple-negative breast cancer (TNBC) is a biologically aggressive tumour, characterised by high rates of metastasis. Improved chemotherapeutic approaches against BC are therefore an urgent clinical need. In this study, complexes with two and three metal centres linked by the biogenic polyamines: putrescine (Pt2Put2(NH3)4 and Pd2Put2) and spermidine (Pt3Spd2 and Pd3Spd2), as well as cisplatin were tested against non-malignant (MCF- 12A), a TNBC (MDA-MB-468) and a non-TNBC (MCF-7) human cell lines by 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide assay. Fourier transform infrared and Raman microspectroscopies allow to probe biological samples with unmatched subcellular spatial resolution. The results revealed that the polynuclear complexes showed activity for the TNBC cell line. While Pd3Spd2 showed significant impact on DNA (B-DNA toA-or Z-DNA), Pt2Put2(NH3)4 had a stronger effect on proteins (seen through Amide II vibrational mode) . In addition, these complexes exhibited a greater impact on δC=C–H from phospholipids and CH2 deformations from lipids. For non-TNBC, Pd3Spd2 also displayed a strong contribution from Z-DNA (νOPObackbone), whereas Pt2Put2(NH3)4 had a significant impact on Amide I and Amide III signals. This knowledge is expected to contribute for the rational design of improved anticancer drugs, with a higher efficiency coupled to lower toxicity. 1 | Introduction According to the World Health Organization (WHO) [1], it is estimated that 2.6 million new cases of breast cancer will occur in 2030, representing, globally, an increase of 18% since 2020. Due to its high degree of heterogeneity, breast cancer is a neoplasm that can be classified into multiple categories based on its structural organisation and morphology. The presence of biomarkers such as the oestrogen receptor (ER), the progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) determines the types and subtypes of breast cancer: ER+ (ER+/ HER2 − ), HER2+ (ER − /HER2+), triple-negative (ER− /PR − /HER2 − ) and triple-positive (ER+/PR+/HER2+) . It can also be subdivided into basal-like, luminal (luminal A and luminal B), normal-like, HER2-enriched and claudin-low subtypes [2, 3] . Currently, the luminal androgen receptor (LAR), basal-like immune-activated (BLIA), basal-like immune-suppressed (BLIS) and mesenchymallike (M) subtype classifications of triple-negative breast cancer (TNBC) are widely accepted [4, 5]. Since it lacks expression of ER, PR and HER2 (ER − /PR − /HER2 − ), TNBC does not respond to hormone therapy. Hence, it is associated with the poorest prognosis within breast cancers, whereas non-TNBC subtypes—particularly oestrogen receptor-positive (ER+) tumours—are generally linked to more favourable overall survival outcomes. TNBC is the most aggressive breast cancer subtype, characterised by higher incidence and mortality rates, and is more frequently observed in younger and premenopausal women [6–8] . This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits

FAQs

What experimental approach was used to test the Pd and Pt complexes?

Cell viability was assessed using the MTT assay on MCF-12A, MDA-MB-468 (TNBC) and MCF-7 (non-TNBC) cell lines. Biological effects were further probed with Fourier transform infrared (micro-FTIR) and Raman microspectroscopies for subcellular spatial insight.

Which complexes showed activity against the TNBC cell line?

The polynuclear complexes displayed activity for the TNBC cell line. Pd3Spd2 produced a significant impact on DNA conformation (B-DNA to A- or Z-DNA), while Pt2Put2(NH3)4 showed a stronger effect on proteins via the Amide II vibrational mode.

How did the complexes affect biomolecular signals in non-TNBC cells?

For non-TNBC cells, Pd3Spd2 showed a strong contribution from Z-DNA signals (νOPObackbone), whereas Pt2Put2(NH3)4 significantly influenced Amide I and Amide III signals. These differential spectral effects support distinct molecular interactions across TNBC and non-TNBC contexts.

Sep 22, 2026

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