Neutrophil Camouflaged Stealth Nanovehicle for Photothermal-Induced Tumor Immunotherapy by Triggering Pyroptosis

The regulation of tumor immunosuppressive microenvironments via precise drug delivery is a promising strategy for preventing tumor recurrence and metastasis. Inspired by the stealth strategy, a stealthy nanovehicle based on neutrophil camouflage is developed to achieve precise delivery and tumor immunotherapy by triggering pyroptosis. The nanovehicle comprises anti-CD11b- and IR820-conjugated bovine serum albumin nanoparticles loaded with decitabine. Camouflaged by neutrophils, the nanovehicles achieve efficient tumor delivery by neutrophil hitchhiking owing to the biotropism of neutrophils for tumors. The fluorescent signal molecule, IR820, on the nanovehicle acts as a navigation monitor to track the precise delivery of the nanovehicle. The released decitabine upregulates gasdermin E, and laser irradiation activates caspase-3, thereby resulting in pyroptosis, which improves the system's adaptive immune response. In a triple-negative breast cancer animal model, it regulates the immunosuppressive microenvironment for effective tumor immunotherapy and induces a long-lasting and strong immune memory to prevent lung metastasis.

Automated summary

Regulating tumor immunosuppressive microenvironments through precise drug delivery is a promising strategy for preventing tumor recurrence. A nanovehicle that camouflages with neutrophils has been developed to achieve precise delivery and tumor immunotherapy. The nanovehicle, loaded with decitabine, takes advantage of the biotropism of neutrophils for tumors to efficiently deliver the drug. It also includes a fluorescent signal molecule for tracking the delivery, and triggers pyroptosis to enhance the immune response. In animal models, it effectively regulates the immunosuppressive microenvironment and prevents lung metastasis.