Coupling Probiotics with CaO2 Nanoparticle‐Loaded CoFeCe‐LDH Nanosheets to Remodel the Tumor Microenvironment for Precise Chemodynamic Therapy

Chemodynamic therapy (CDT) has become an emerging cancer treatment strategy with advantages of tumor-specificity, high selectivity, and low systemic toxicity. However, it usually suffers from low therapeutic efficacy. This is caused by low hydroxyl radical (·OH) yield arising because of the relatively high pH, overexpressed glutathione, and low H2O2 concentration in the tumor microenvironment (TME). Herein, a probiotic metabolism-initiated pH reduction and H2O2 supply-enhanced CDT strategy is reported to eradicate tumors by generating ·OH, in which Lactobacillus acidophilus is coupled with CoFeCe-layered double hydroxide nanosheets loaded with CaO2 nanoparticles (NPs) as a chemodynamic platform for high-efficiency CDT (CaO2/LDH@L. acidophilus). Owing to the hypoxia tropism of L. acidophilus, CaO2/LDH@L. acidophilus exhibits increased accumulation at tumor sites compared with the CaO2/LDH. The CaO2 NPs loaded on CoFeCe-LDH nanosheets are decomposed into H2O2 in the TME. L. acidophilus metabolite-induced pH reduction (<5.5) and CaO2-mediated in situ H2O2 generation synergistically boost ·OH generation activity of the CoFeCe-LDH nanosheets, effectively damaging cancer cells and ablating tumors with a tumor inhibition rate of 96.4%, 2.32-fold higher than that of CaO2/LDH. This work demonstrates that probiotics can function as a tumor-targeting platform to remodel the TME and amplify ROS generation for highly efficient and precise CDT.