A piezoelectric catalytic cascade nanoreactor which reshapes the tumor microenvironment and promotes effective multi-dimensional therapy.

The nature of the tumor microenvironment (TME) is often a hindrance to effective cancer therapy and results in treatment failure. Here, a nanoparticle cascade catalyst has been developed. This platform, Ber/CoFe 2 O 4 @PSiO 2 -KCN, is based on CoFe 2 O 4 nanoparticles which are then coated with silica, functionalized with potassium doped carbon nitride (KCN) and loaded with the drug berberine (Ber). Ber/CoFe 2 O 4 @PSiO 2 -KCN in combination with ultrasound is found to have the ability to generate gluconic acid and H 2 O 2 from glucose and convert H 2 O 2 to ·OH to provide effective chemodynamic therapy. Ber promotes the accumulation of lactic acid in tumor cells, acidifying the TME and facilitating the catalytic reactions of KCN and CoFe 2 O 4. The oxidative stress generated by the presence of large amounts of ·OH in the tumor triggers cell apoptosis, the production of damage-associated molecular pathways, and thus induces immunogenic cell death. The potent anti-tumor effects and imaging function of Ber/CoFe 2 O 4 @PSiO 2 -KCN could be applied as a future anti-cancer therapy. [Display omitted] • Multifunctional nanoparticles (NPs) are developed to enhance cancer therapy. • The NPs can catalyze the conversion of glucose to gluconic acid for starvation therapy. • The NPs further catalyze the production of reactive oxygen species. • In vitro and in vivo results evidence synergistic death of cancer cells. [ABSTRACT FROM AUTHOR]