Metallodrugs: Synthesis, mechanism of action and nanoencapsulation for targeted chemotherapy

As a multifactorial and heterogeneous disease, cancer has a high mortality rate, and the search for more effective treatments is an enormous challenge. Metal coordination compounds open a range of possibilities that conventional organic and biological molecules can no longer fulfil due to increasing drug resistance. Metallodrugs still have tremendous potential to help overcome drug resistance and find new cures in medicine, considering that at least 25 metallic elements participate in healthy functioning of the human body. Transition metal ions, such as copper, zinc and iron, are incorporated into catalytic proteins, the so-called metalloenzymes, which participate in various chemical reactions necessary for life. The interaction of metal complexes in different pathways with the structural richness of deoxyribonucleic acid encouraged to seek to understand the mechanisms of action and overcome the obstacles encountered for a promising future of these drugs. The success of platinum-based metallodrugs is one of the great inspirations for the search of new metallodrugs, although the approval of these molecules has been slow in recent years due to the risk of systemic toxicity and insufficient understanding of their mechanisms. To overcome the clinical limitations encountered in some metallodrugs, nanoencapsulation has been proposed as a new approach to improve therapeutic index in chemotherapy. The remarkable selectivity of nanoencapsulated metallodrugs and their enhanced capacity to bypass various biological barriers allow site-specific targeting. In this review, we present the advances in the development and use of the most relevant metallodrugs, and new delivery approaches, in the fight against cancer.