Self-assembled nanoparticle-mediated cascade chemotherapy and chemodynamic therapy for enhanced tumor therapy

Chemodynamic therapy (CDT) is a non-invasive treatment strategy that aims to combat tumor growth by efficiently generating reactive oxygen species (ROS). However, the effectiveness of CDT can be limited by factors such as the availability of endogenous hydrogen peroxide (H 2 O 2 ). Here, we established an intelligent nano-based drug delivery system responsive to the tumor microenvironment by self-assembling Cu 2 + , cisplatin, and L-histidine to form nanoparticles (Pt/CuH NPs), which can achieve the therapeutic effect of specific tumor killing by cascading chemotherapy with CDT. The Pt/CuH NPs are triggered by the acidic conditions and high glutathione (GSH) levels present in the tumor microenvironment, leading to the release of cisplatin and Cu 2 + . Cisplatin facilitates the production of H 2 O 2 through a two-step enzymatic reaction, subsequently triggering ROS cascade that is amplified by CDT. Concurrently, Cu 2 + consumes GSH and is reduced to Cu + , which reacts with H 2 O 2 in an efficient Fenton-like reaction, amplifying oxidative stress and ultimately enhancing the anti -tumor therapeutic efficacy. Pt/CuH NPs demonstrated a significant cytotoxic effect on tumor cells in vitro. In vivo studies in mice indicated minimal toxic side effects at the tested dosages. The Pt/CuH NPs effectively combine chemotherapy and CDT strategies, showcasing the potential of a chemotherapy -cascading CDT approach for anti -tumor treatment.