Functionalization and cancer-targeting design of ruthenium complexes for precise cancer therapy

The successful clinical application of the three generation platinum anticancer drugs, cisplatin, carboplatin and oxaliplatin, has promoted research interest in metallodrugs; however, the problems of drug resistance and adverse effects have hindered their further application and effects. Thus, scientists are searching for new anticancer metallodrugs with lower toxicity and higher efficacy. The ruthenium complexes have emerged as the most promising alternatives to platinum-based anticancer agents because of their unique multifunctional biochemical properties. In this review, we first focus on the anticancer applications of various ruthenium complexes in different signaling pathways, including the mitochondria-mediated pathway, the DNA damage-mediated pathway, and the death receptor-mediated pathway. We then discuss the functionalization and cancer-targeting designs of different ruthenium complexes in conjunction with other therapies such as photodynamic therapy, photothermal therapy, radiosensitization, targeted therapy and nanotechnology for precise cancer therapy. This review will help in designing and accelerating the research progress regarding new anticancer ruthenium complexes.