Surface-Layer Protein-Enhanced Immunotherapy Based on Cell Membrane-Coated Nanoparticles for the Effective Inhibition of Tumor Growth and Metastasis.

Chemo-immunotherapy is an important tool to overcome tumor immune suppression in cancer immunotherapy. Herein, we report a surface-layer (S-layer) protein-enhanced immunotherapy strategy based on cell membrane-coated S-CM-HPAD nanoparticles for the effective malignant tumor therapy and metastasis inhibition. The S-CM-HPAD NPs could effectively deliver the tumor antigen, DOX, and immunoadjuvant to the homotypic tumor by the homotypic targeting ability of the coated cell membrane. In addition to its ability to induce tumor cell death, the loaded DOX could enhance the immunotherapy response by inhibition of myeloid-derived suppressor cells (MDSCs). Because of the intrinsic adjuvant property and capability to surface display epitopes and proteins, the S-layers localized on the surface of S-CM-HPAD NPs potentiated the immune response to the antigen. The results confirmed that the protective immunity against tumor occurrence was promoted effectively by prompting proliferation of lymphocytes and secretion of cytokine caused by the tumor-associated antigen and adjuvant. The excellent combinational therapeutic effects on the inhibition of tumor growth and metastasis in the melanoma tumor models demonstrated that the S-layer-enhanced immunotherapeutic method is a promising strategy for tumor immunotherapy of malignant tumor growth and metastasis.