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

Abstract

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.