STING-engineered biomimetic hybrid membrane nanovaccine for enhanced immunotherapy of cervical cancer.

Cancer immunotherapy based on nanovaccines aims to elicit specific anti-tumor immune responses, demonstrating significant therapeutic potential. However, its clinical translation remains hindered by two major challenges: inadequate immunogenicity of the vaccine itself and limited antigen presentation efficiency in dendritic cells (DCs). To overcome these bottlenecks, we have developed a biomimetic nanovaccine for cervical cancer treatment. This vaccine employs a sophisticated biomimetic design: its core consists of iron oxide nanoparticles that serve as both an immune adjuvant and a carrier for the STING agonist DMXAA; the core is enveloped by a hybrid membrane formed by fusing cancer cell membranes (carrying a complete set of tumor-associated antigens) with bacterial membranes (rich in natural immune adjuvants); and the outermost layer is further functionalized with mannose ligands for specific targeting of DCs in the lymph nodes. This multi-layered architecture achieves exceptional synergistic immune activation: the hybrid membrane not only provides a personalized antigen repertoire but also, through its bacterial components, acts as a natural adjuvant to robustly activate innate immunity; upon external stimulation, the core synchronously releases the STING agonist, efficiently activating the cytosolic STING pathway and significantly amplifying the production of type I interferons and related cytokines, thereby shaping a potent anti-tumor immune microenvironment; meanwhile, the mannose-mediated active targeting ensures efficient uptake of the vaccine by DCs in the lymph node sinuses, ultimately greatly promoting antigen cross-presentation and the activation and proliferation of cytotoxic T lymphocytes. In vivo experimental results demonstrate that this nanovaccine can significantly inhibit tumor progression in mouse models of cervical cancer and effectively prevent tumor recurrence. This study provides a novel and translationally promising strategy for the development of highly effective and personalized cancer immunotherapy platforms.