Pt(II)‐Phenanthroline‐Ln(III)‐DOTA d–f Hybrids as Small‐Molecule Theranostics

1,10‐Phenanthroline d‐ or f‐metal complexes can be utilised in biomedical applications such as imaging or therapeutics. Herein, we designed bimetallic d‐block metal‐phenanthroline f‐block metal‐1,4,7,10‐tetraazacyclododecane‐1,4,7,1,0‐tetraacetic acid (DOTA) conjugates as theranostic agents to simultaneously achieve both of these applications. Luminescence studies show the 1,10‐phenanthroline‐Eu(III)‐DOTA complexes displayed an off/on/off pH‐dependent switch, demonstrating their potential as pH‐responsive lanthanide luminescence probes. Relaxometry studies showed that the 1,10‐phenanthroline‐Gd(III)‐DOTA complexes present a r1 of 5.15±0.05 mM−1 s−1 and could thus be used as magnetic resonance (MR) contrast agents. Complexation of Pt(II) by the 1,10‐phenanthroline moiety resulted in quenching of the Eu(III) luminescence, but an enhancement of the Gd(III) relaxivity (r1=7.53±0.69 mM−1 s−1). Cell viability studies of the d–f hybrids in a cancer cell line showed the potential of these complexes as anticancer agents, as the IC50 for the Pt(II)/Gd(III) complex (IC50=24.9 μM) was lower than that of cisplatin (IC50=31.6 μM). As such, Pt(II)‐1,10‐phenanthroline‐Gd(III)‐DOTA complexes are promising theranostic agents for cancer therapy. The synthesis of d‐block metal‐phenanthroline lanthanide complexes as theranostics for cancer therapy is described. The phenanthroline‐Eu(III)‐DOTA complexes displayed an off/on/off pH‐dependent luminescence switch, and the Gd(III) complexes exhibited high r1, meaning that these probes can be used for in vitro/in vivo lanthanide luminescence or MRI. Following complexation with Pt(II), the Gd(III) complex had higher cytotoxicity than cisplatin, making it a promising anticancer MR theranostic.