A gold cluster fused manganese dioxide nanocube loaded with dihydroartemisinin for effective cancer treatment via amplified oxidative stress

Abstract

Chemodynamic therapy, leveraging metabolic processes for reactive oxygen species (ROS) generation, shows promise in cancer eradication. However, its efficacy is hampered by hypoxic conditions, substrate scarcity, and abundant ROS scavengers. In this study, we have devised a cubic manganese oxide nanozyme (BSA–AuNC–MnO₂@DHA) to tackle these obstacles. This nanozyme integrates MnO₂ with bovine serum albumin (BSA)-coated gold nanoclusters (AuNC), forming BSA–AuNC–MnO₂, and further incorporates dihydroartemisinin (DHA) to confer both bioimaging and anticancer capabilities. The BSA–AuNC–MnO₂ nanoparticles exhibit a uniform cubic morphology, with an average hydrated particle diameter of 76.4 ± 7.1 nm and a zeta potential of −32.6 mV, indicative of their excellent dispersion and stability. The encapsulation efficiency of DHA within the BSA–AuNC–MnO₂@DHA system achieved a remarkable value of 72.45%, attesting to its substantial drug-loading capacity. MnO₂ serves a dual function within the nanozyme: it augments oxidative stress while concurrently inhibiting antioxidant defenses. It depletes the antioxidant glutathione (GSH) to release Mn²⁺, which in turn catalyzes ROS production from intracellular substrates and DHA. The remarkable anticancer efficacy of this tailored approach is evidenced by the potent inhibition of tumor growth observed after a single-dose administration, which underscores the amplification of oxidative stress. Additionally, BSA–AuNC–MnO₂@DHA exhibits negligible toxicity to major organs, highlighting its exceptional biocompatibility and safety profile.