Drug-device-field integration for tumor therapeutic interference with home-tailored nano-heterojunctions

Sonodynamic therapy has exhibited tremendous merits such as deep tissue penetration, minimal invasiveness, and neglectable side effects, but the strong O₂ dependence and complex tumor microenvironment limit the therapy efficiency. Herein, a type of BaTiO₃@MnO₂-based Z-scheme nano-heterojunction has been conjugated to doxorubicin-loaded carbon nanotubes to form functionalized hybrid nanocomposites for O₂-independent and TME-modulating combinational tumor therapy. The existences of BaTiO₃ and MnO₂ afford a built-in microelectric field which induces band tilting to effectively transfer electrons with a Z-scheme track, prolonged the electron–hole separation lifetime, and maintained strong redox potentials for hydrolysis and abundant reactive oxygen species generation. The in vivo experiments prove that nano-heterojunctions actively accumulate at the tumor after intravenous injection and demonstrate a glutathione-responsive behavior to impair tumor anti-oxidant and enhance ROS contents. It was also noted that the ultrasound-mediated treatment in association with nano-heterojunctions showed a superior O₂-independent tumor elimination (up to 90%) in company with dramatic recruitments of CD4⁺ and CD8⁺ T cells. Therefore, this study has validated the BaTiO₃@MnO₂-based Z-scheme nano-heterojunctions with tumor therapeutic interference in a drug-device-field integration manner and highlighted their promising utilities for modulating the tumor microenvironment and overcoming the O₂ dependence for an efficacious tumor therapy in live animals.