In Situ Self‐Aggregation of Spirulina Skeleton Fibers Enhances the Efficacy of Anti‐Tumor Thermal Immunotherapy

Abstract The lack of broad‐spectrum tumor antigens, limited immunogenicity of antigens, and immunosuppressive microenvironment in tumors have impeded the development of cancer vaccines. To address this issue, a vaccine platform is developed based on Spirulina skeleton fibers loaded with gold (Au) nanoparticles (Au@E‐SP). Upon subcutaneous administration, Au@E‐SP self‐aggregates in situ and forms a 3D vaccine scaffold owing to its elongated and helical architecture. Through the aggregation of Au@E‐SP, Au nanoparticles are concentrated, which significantly enhances the local photothermal effect and releases more tumor‐associated antigens. In addition, the retained E‐SP serves as a natural immune adjuvant that sustainably reverses the immunosuppressive microenvironment in vivo. Combining these advantages, the vaccines induce a potent anti‐tumor immune response, effectively inhibiting tumor recurrence and metastasis. This strategy utilizes microalgae as a self‐adjuvant vaccine, providing a promising avenue for further research in tumor immunotherapy.