Ruthenium (II)-coordinated supramolecular drug self-assembly for efficient combination chemotherapy

Combination chemotherapy has been considered a crucial approach in cancer treatment to address the limitations of traditional single-drug therapy. However, the common strategies that encapsulate therapeutic agents with different mechanisms into a single “package” often lead to unsatisfactory anticancer activity because of the relatively low loading capacities, inconsistent reproducibility, and unpredictable release kinetics. In this study, we reported the construction of ruthenium (II)-coordinated supramolecular drug self-delivery systems. These systems are proposed to provide a stable and efficient transport platform for delivering drugs, thereby enhancing the effectiveness of combination chemotherapy. Ruthenium (II)-coordinated supramolecular polymer (RuSP) was first formed through host-guest interaction between β-cyclodextrin (β-CD) units grafted onto a hyaluronic acid chain (HA-CD) and (Benzene)Ru(curcuminato)Cl (Ru-Cur). The obtained RuSP then further self-assembled into ruthenium (II)-coordinated supramolecular drug self-assemblies (RuSDSAs). Upon internalization into cancer cells, RuSDSAs could be effectively degraded in acidic tumor microenvironment as for the smart dissociation of host-guest interaction, allowing for the controlled release of Ru-Cur and enhancing the efficacy of combination chemotherapy. Biological evaluation demonstrated that RuSDSAs achieved good anticancer effects and are biologically safe.