Mitochondria-targeted and ROS-sensitive main-chain ruthenium polymer overcomes cancer drug resistance

The clinical efficacy of platinum-based chemotherapeutics, such as cisplatin, has been compromised by the prevalent emergence of drug resistance. This has propelled the search for alternative metal-based anti-tumor agents. Herein, we introduce PolyRu, a novel amphiphilic polymer containing a ruthenium complex and thioketal bonds in its main chain, for lung cancer treatment. PolyRu can self-assemble into nanoparticles (NP@PolyRu) in aqueous solutions and degrade within the reactive oxygen species-rich tumor microenvironment. The ruthenium complex in PolyRu specifically targets mitochondria and induces cancer cell apoptosis. The efficacy of NP@PolyRu was validated in a patient-derived xenograft model of human lung cancer, where NP@PolyRu significantly suppressed tumor progression with favorable biocompatibility，and showed excellent anti-tumor immune effect. NP@PolyRu emerges as a promising candidate for addressing cancer drug resistance, signifying a substantial leap forward in the realm of metal polymer-based cancer therapeutics.