Nanoenzyme-Augmented Cancer Sonodynamic Therapy by Catalytic Tumor Oxygenation

Ultrasound (US)-triggered sonodynamic therapy (SDT) can solve the critical issue of low tissue-penetrating depth of traditional phototriggered therapies, but the SDT efficacy is still not satisfactorily high in combating cancer at the current stage. Here we report on augmenting the SDT efficacy based on catalytic nanomedicine, which takes the efficient catalytic features of nanoenzymes to modulate the tumor microenvironment (TME). The multifunctional nanosonosensitizers have been successfully constructed by the integration of a MnOx component with biocompatible/biodegradable hollow mesoporous organosilica nanoparticles, followed by conjugation with protoporphyrin (as the sonosensitizer) and cyclic arginine-glycine-aspartic pentapeptide (as the targeting peptide). The MnOx component in the composite nanosonosensitizer acts as an inorganic nanoenzyme for converting the tumor-overexpressed hydrogen peroxide (H2O2) molecules into oxygen and enhancing the tumor oxygen level subsequently, which has been demonst...