pH-Responsive Cascaded Nanocatalyst for Synergistic Like-Starvation and Chemodynamic therapy

A tumor microenvironment (TME) responsive cascade nanocatalyst was built based on copper-embedded hollow mesoporous silica (HMSN-Cu) decorated with glucose oxidase (GOD) on the surface, realizing tumor-selected cascade catalyst for elegant combination of starving therapy and chemodynamic therapy. Specifically, benefited from the strong demand for glucose metabolism in tumor cells, this HMSN-Cu-GOD could catalyze rich glucose into H₂O₂ in the presence of O₂, along with localized declined pH in situ to in turn degrade HMSN-Cu and thus release Cu²⁺/Cu⁺. Importantly, abound hydroxyl radical (•OH) with high oxidative activity generated in the Fenton reaction between H₂O₂ and Cu²⁺/Cu⁺. Interesting, the high-expressed GSH and exacerbated hypoxia in tumor cells, will facilitate accumulation of Cu⁺ with much higher reaction efficiency, further enhanced Chemodynamic therapy (CDT) efficiency. Compared with monotherapy, in vitro and vivo tumor inhibition experiments demonstrated the superior synergistic effect of CDT and starving therapy based on a simple but effective biodegradable nanosystem.