Engineered biohybrids for photothermally enhanced chemodynamic-immunotherapy through reprograming immunosuppressive microenvironment and inhibiting immune evasion.

The therapeutic effect of chemodynamic-immunotherapy is limited by the insufficient hydroxyl radical generation and immunesuppressive tumor microenvironment. Here, an engineered Escherichia coli was designed to co-express lactate oxidase (LOX) and programmed death 1 (PD1) protein on its surface. Then the engineered bacteria were modified with copper sulfide nanoparticles to develop the biohybrid (denoted as BLPC). The LOX expressed on BLPC could consume lactate to generate hydrogen peroxide. Under near-infrared light irradiation, the photothermal effect of copper sulfide nanoparticles can further promote the efficacy of the Fenton reaction and enhance chemodynamic therapy, thereby inducing effective immunogenic cell death and activating immune responses. At the same time, the consumption of lactate could reverse immunosuppressive tumor microenvironment. Furthermore, PD1 protein expressed on BLPC would inhibit immune evasion by blocking the programmed cell death ligand 1 (PD-L1)/PD1 pathway, further enhancing the immunotherapy. Therefore, this engineered biohybrid provided a promising strategy for multimodal therapy of triple-negative breast cancer.