Hybrid membrane nanosystems for cancer immunotherapy: Biomimetic design, immune activation, and translational...

Conventional nanocarriers used in cancer immunotherapy face intrinsic limitations, such as suboptimal targeting efficiency, rapid reticuloendothelial clearance, and insufficient functionality, which have severely hindered the clinical translation of immunotherapeutic agents. Hybrid membrane-based biomimetic nanosystems have emerged as a promising solution to overcome these constraints by integrating the biological properties of heterogeneous cell membrane components to achieve synergistic functions encompassing "long circulation-active targeting-immune regulation". This represents an innovative strategy for combinatorial cancer immunotherapy. Herein, the construction strategies and technological advancements in hybrid membrane-based nanosystems are systematically outlined. We detail the selection criteria and biological properties of membrane materials derived from diverse sources, such as red blood cell membranes, cancer cell membranes, platelet membranes, and immune cell membranes, along with the construction strategies for the corresponding nanoparticles. Building on this foundation, this review elucidates the biological properties and construction strategies of hybrid membrane nanosystems from the perspective of their combinatorial functions, with a particular focus on the synergistic mechanisms of commonly used hybrids, such as red blood cell-cancer cell, platelet-cancer cell, and immune cell-cancer cell membrane hybrids. Furthermore, a comprehensive overview of the cutting-edge applications of these nanosystems is provided, highlighting their roles in inducing immunogenic cell death, remodeling the immunosuppressive tumor microenvironment, potentiating immune checkpoint blockade therapy, and developing personalized cancer vaccines. Finally, current technical and biological challenges are critically analyzed to offer perspectives on future directions in this evolving field.