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/CoFe2O4@PSiO2-KCN, is based on CoFe2O4 nanoparticles which are then coated with silica, functionalized with potassium doped carbon nitride (KCN) and loaded with the drug berberine (Ber). Ber/CoFe2O4@PSiO2-KCN in combination with ultrasound is found to have the ability to generate gluconic acid and H2O2 from glucose and convert H2O2 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 CoFe2O4. 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/CoFe2O4@PSiO2-KCN could be applied as a future anti-cancer therapy.