Cascade catalytic nanoplatform for enhanced starvation and sonodynamic therapy

Background: Sonodynamic therapy (SDT) has emerged as an alternative to the traditional treatments of cancer. However, the oxygen consumption induced by SDT and glucose oxidase (GOx) mediated starvation therapy would worsen the hypoxic tumor environment, which further impeded therapeutic efficacy. Purpose: To develop a nanoplatform and investigate its anti-cancer mechanism for enhanced starvation and SDT.Methods: We constructed a cascade catalytic nanoplatform based on GOx modified the mesoporous MnO₂ NPs loaded with hematoporphyrin monomethyl ether (HMME), which were designated as GOx-MnO₂/HMME. We characterized them for their catalytic activity, and investigate the magnetic resonance imaging and anti-tumor efficiency in vitro and in vivo.Results: MnO₂ NPs with catalase-like activity could oxidize H₂O₂ under acid condition to produce O₂, which not only in turn was supplied to the glucose-depletion reaction for an efficient starvation therapy, but also enhanced the ¹O₂ generation for HMME mediated SDT effect. In addition, the released Mn²⁺ ions in the system were able to enhance the MRI signal. Both in vitro and in vivo experiments suggested the cascade catalytic-therapeutic effect between GOx, MnO₂ NPs and HMME, demonstrating the enhanced starvation and SDT.