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.