Platinum-containing heterometallic complexes in cancer therapy: advances and perspectives

Abstract

Platinum-based anticancer drugs are among the most widely used antineoplastics in clinical settings. Their therapeutic applications and outcomes are, however, greatly hampered by drug resistance, systemic toxicity, and the lack of antimetastatic and diagnostic properties. The incorporation of second metal centers with distinct biological targets and favorable physical and chemical properties into platinum complexes is a promising strategy to improve the anticancer efficacy of platinum drugs and overcome their shortcomings. This review focuses on Pt-containing heterometallic complexes Pt–M (M = Ru, Au, Ti, Fe, Rh, Pd, Cu, Ir, Gd, Eu, Re, and Tc) for cancer therapy. The design, anticancer activities, mechanism of action, and interplay between Pt and the second metal center are discussed. Many dual-pharmacophore heterometallic complexes have shown a great potential for overcoming cisplatin resistance. Besides, the incorporation of Ru(III) or areneRu(II) moieties into Pt complexes has been proved to inhibit cancer metastasis effectively. Moreover, theragnostic heterometallic complexes have been obtained by combining cytotoxic Pt and luminescent Eu(III), MRI responsive Gd(III), or radioactive ^99mTc(I) into a single molecule. We also discuss the photophysical and bioimaging properties of theragnostic heterometallic complexes. This review provides a comprehensive landscape of representative examples of Pt-containing heterometallic complexes investigated in the last decade for cancer therapy and may guide researchers in exploring the challenges and opportunities in this emerging field.