Clara B. Martins, M P Marques, Luís Carvalho, Ana L. M. Batista de Carvalho
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 (Pt 2 Put 2 (NH 3 ) 4 and Pd 2 Put 2 ) and spermidine (Pt 3 Spd 2 and Pd 3 Spd 2 ), 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 sub‐cellular spatial resolution. The results revealed that the polynuclear complexes showed activity for the TNBC cell line. While Pd 3 Spd 2 showed significant impact on DNA (B‐DNA to A‐ or Z‐DNA), Pt 2 Put 2 (NH 3 ) 4 had a stronger effect on proteins (seen through Amide II vibrational mode). In addition, these complexes exhibited a greater impact on δ C =C–H from phospholipids and CH 2 deformations from lipids. For non‐TNBC, Pd 3 Spd 2 also displayed a strong contribution from Z‐DNA ( ν OPO backbone ), whereas Pt 2 Put 2 (NH 3 ) 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.