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

Abstract

Abstract1,10‐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.