Tumor Cell Membrane-Engineered MXene Nanoplatform for Chemo-Photothermal Immunotherapy of Bladder Cancer

Abstract

Bladder cancer is a major clinical challenge due to high recurrence and limited efficacy of conventional therapies, creating an urgent demand for localized and targeted strategies. In this study, we developed a tumor cell (MB49) membrane-coated Ti₃C₂Tₓ MXene nanoplatform loaded with doxorubicin (MXene@TCM-DOX) for synergistic chemo-photothermal therapy and immune activation. MXene@TCM-DOX displayed excellent photothermal performance, favorable biocompatibility, and enhanced tumor-targeting capability. Therapeutic efficacy was evaluated in bladder cancer cells, human tumor organoids, and subcutaneous and orthotopic mouse bladder cancer models. Biological analyses revealed that MXene@TCM-DOX significantly induced tumor cell apoptosis and inhibited tumor growth more effectively than monotherapy. Notably, the nanoplatform promoted CD8⁺ T cell infiltration and activation with upregulated granzyme B and perforin expression, thereby enhancing antitumor immune responses. This study demonstrates that MXene@TCM-DOX integrates chemo-photothermal therapy and immune activation, providing a promising localized strategy for bladder cancer treatment.