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.