Genetically engineered hybrid membrane-coated nanoparticles enable triple activation of dendritic cells for synergistic bladder cancer immunotherapy

Limited lymphocyte infiltration and insufficient tumor immunogenicity remain major challenges for effective immunotherapy in bladder cancer, particularly in immunologically “cold” tumors with a highly suppressive immune microenvironment. Effective activation of the innate immune system is critical for initiating a robust adaptive anti-tumor immune response, primarily mediated by dendritic cells (DCs). Here, we designed genetically engineered hybrid membrane-coated nanoparticles (HM-MPS NPs) with excellent photothermal stability, tumor-targeting capability, and biocompatibility. HM-MPS NPs demonstrated significant tumor-suppressive effects in multiple preclinical models, including murine subcutaneous, orthotopic, and distant bladder tumor models. By combining photothermal therapy (PTT), a STING agonist (SR717), and antigen presentation, HM-MPS NPs achieve triple activation of DCs, leading to enhanced T-cell activation and a remodeled immune microenvironment. Furthermore, HM-MPS NPs synergize effectively with anti-PD-1 therapy, amplifying immunogenic cell death (ICD) and overcoming immune suppression within the tumor microenvironment. This strategy significantly boosts tumor immunogenicity and enhances anti-tumor immune responses, offering a promising approach for bladder cancer treatment.