Cancer immunotherapy has reshaped the landscape of cancer treatment. However, its efficacy is still limited by tumor immunosuppression associated with the excessive production of lactate by cancer cells. Although extensive efforts have been made to reduce lactate concentrations through inhibition of lactate dehydrogenase, such inhibitors disrupt the metabolism of healthy cells, causing severe nonspecific toxicity. We report herein a nanocapsule enzyme therapeutic based on lactate oxidase, which reduces lactate concentrations and releases immunostimulatory hydrogen peroxide, averting tumor immunosuppression and improving the efficacy of immune checkpoint blockade treatment. As demonstrated in a murine melanoma model and a humanized mouse model of triple-negative breast cancer, this enzyme therapeutic affords an effective tool toward more effective cancer immunotherapy.

Guided bone regeneration (GBR) is a standard therapy for treating bone defects, with collagen-based barrier membranes widely used clinically. However, these membranes face challenges like poor mechanical properties, early bacterial invasion and immunomodulation deficiency, potentially risking GBR failure. Orchestrating macrophage activation and controlling their M1 or M2 polarization are effective strategies for bone repair. Here, we present a Janus collagen-based barrier membrane with immunomodulation. The porous layer promotes direct osteogenic differentiation and inward growth of osteoblasts. The dense layer prevents invasion of soft tissue into bone defects and protects bone defects from bacterial infection. The membrane also enhances rat bone marrow-derived mesenchymal stem cell infiltration, proliferation, and osteogenic differentiation by regulating the immune microenvironment, demonstrating superior bone regeneration compared to the commercial Bio-Gide® membrane. Overall, the Janus collagen-based membrane reduces tissue inflammation and fosters an osteoimmune environment conducive to new bone formation, offering effective material design for advanced GBR technology.