Recent Development of Metallopharmaceuticals in Cancer Therapy: Ruthenium Complexes and Their Analogues

Abstract Traditional chemotherapy has been widely used to treat human malignancies but suffers from major drawbacks such as inherent drug resistance, systemic toxicity, poor selectivity, and significant adverse effects. As a result, the survival rate among chemotherapy patients remains alarmingly low, with only around 5% experiencing long-term success. Platinum (Pt)-based drugs such as cisplatin are commonly used but are often limited by chemoresistance and toxicity toward healthy cells. Consequently, there has been a growing interest in developing novel metallo-anticancer agents that can selectively target cancer cells while minimizing harm to normal tissue. Ruthenium (Ru) complexes have emerged as promising candidates due to their unique redox properties, low toxicity, and the ability to mimic iron in binding biological molecules. They have demonstrated potent anticancer and anti-metastatic properties and have been explored in advanced treatment strategies such as photodynamic therapy (PDT) and photoactivated chemotherapy (PACT), which offer spatial control over drug activation. Several Ru-based compounds, such as NAMI-A, KP1019, KP1339, and TLD-1433, have progressed into clinical trials, alongside arene complexes like RM175 and RAPTA-C. With ongoing research and the integration of these complexes into macromolecular matrices, Ru-based drugs hold significant promise as next-generation anticancer therapies.