Composite bioreactor for synergistic Modulation of tumor microenvironment and endogenous Regulation of ROS generation to enhance chemodynamic therapy for lung cancer.

The tumor microenvironment (TME) is characterized by several key features, including hypoxia, elevated levels of hydrogen peroxide (HO), high concentrations of glutathione (GSH), and an acidic pH. Recent research has increasingly focused on harnessing or targeting these characteristics for effective cancer therapy. In this study, we developed an innovative composite bio-reactor that integrates genetically engineered bacteria with upconversion nanoparticles (UCNPs) and nano-copper manganese materials for lung cancer treatment. The nano-copper manganese materials function as catalysts in Fenton-like reactions, facilitating the decomposition of hydrogen peroxide into harmful hydroxyl radicals and oxygen, which can effectively target tumors and reduce hypoxia. To circumvent the challenge of insufficient endogenous hydrogen peroxide during treatment, we employed UCNPs capable of converting near-infrared laser irradiation, known for its deep tissue penetration, into visible light. This conversion activates the genetically engineered bacteria to generate exogenous hydrogen peroxide directly within the tumor microenvironment, enabling prolonged therapeutic effects. Our findings suggest that this composite bio-reactor can achieve effective lung cancer therapy without the need for external hydrogen peroxide supplementation, representing a significant advancement in the design of targeted cancer treatments.