E5 peptide-functionalized platinum nanozymes mediate immune microenvironment reprogramming in B-cell lymphoma

To address the complexity of structural design and synergistic optimization of biological effects of nanozymes in the field of oncology therapy, this study constructed a nanozymes platform (Pt@E5) with a facile and highly efficient preparation process for precision targeting of lymphoma. Pt@E5 nanozymes assemblies were directly prepared by a one-step reduction method, and the modification of E5 peptide ensured the dimensional homogeneity and stability of the platinum nanoparticles. This nano enzymatic platform combines dual enzyme activity with chemokine receptor 4 (CXCR4) targeting. It can inhibit tumor metastasis by targeting CXCR4 and thus specifically blocking the CXCR4/CXCL12 (stromal cell derived factor 1α) signaling pathway. In addition, it induces mitochondria mediated apoptosis and immunogenic cell death (ICD) in tumor cells by catalyzing the production of reactive oxygen species (ROS) using dual enzyme activity. In a mouse lymphoma model, the therapeutic results showed that Pt@E5 treatment effectively remodeled the tumor immunosuppressive microenvironment by promoting cytotoxic T cell infiltration (CTLs) and reducing regulatory T cell (Treg) levels. It also eliminated A20 cells from the bone marrow and peripheral blood, leading to significant tumor regression compared to the control group. In conclusion, this study offers a promising translational strategy for the multifaceted collaborative treatment of diffuse large B-cell lymphoma (DLBCL) based on a simple nanozyme-peptide assembly.