Combination of light and Ru(II) polypyridyl complexes: Recent advances in the development of new anticancer drugs

Ru(II) polypyridyl complexes are a versatile class of compounds to be exploited in the design of photoresponsive anticancer agents. • Ru(II) polypyridyl complexes are suitable tools in the design of PDT and PACT drugs; • PDT and PACT can be potent and complementary approaches in cancer treatments; • Multiple modalities of action can be combined together to achieve improved performances. The increasing impact of cancer on worldwide mortality makes the research of novel chemotherapeutic agents a current and challenging issue. In the recent years, transition metal complexes have attracted much interest in this field, with cisplatin and its analogues being largely employed in the treatment of a variety of cancers. However, several issues, such as scarce selectivity and severe side effects, makes it urgent to develop alternative solutions. In this scenario, Ru(II) polypyridyl complexes (RPCs) have emerged as promising systems to be used in photodynamic therapy (PDT) and, more recently, in photochemotherapy (PACT), taking advantage of the spatio-temporal control over the drug activation ensured by light. Their versatile chemical-physical repertoire may be exploited to design both substitutionally inert photosensitizer agents for PDT and photolabile complexes for PACT, the latter featuring oxygen-independent mechanisms of action, that are of relevance considering the generally hypoxic environment of tumors. Herein, we reviewed the recent opportunities brought by the use of RPCs in PDT and PACT. Our aim was to provide a general and comprehensive overview of the numerous mechanisms of action that are made accessible by these different, but often complementary, approaches, in a work that could be of use to both the experienced scientist as well as the young researcher who approaches this topic for the first time. A particular emphasis is put on those RPCs that were subjected to an in vitro biological evaluation and whose mechanisms of action were, at least partially, disclosed.