A tumor cell membrane (CM)-based biomimetic membrane tumor vaccine is an emerging prevention and treatment strategy in tumor immunotherapy. However, a single CM mostly has a weak immune-boosting effect. Here, a heterogenic fusion membrane tumor vaccine, EV–CM, was successfully constructed by fusing extracellular vesicles (EVs) from S. aureus and CM from B16F10 melanoma cells. Inheriting the advantages of parental components, the EV–CM combines tumor antigens with natural adjuvants that can be used for immunotherapy and can be easily synergistic with complementary therapies. In vivo vaccine tests have shown that EV–CM can activate immune antitumor responses and prevent tumorigenesis. To further enhance the immunotherapeutic and antimetastatic effects of EV–CM, Pt-porphyrin coordination polymer as an immunopotentiator (CPIP) was implanted into an EV–CM nanoplatform (CPIP@EV–CM), which combines localized sonodynamic/chemodynamic therapy-induced immunogenic cell death with heterogenic fusion membrane-mediated antigen-presenting functions. In vitro performance tests, cell experiments, and in vivo animal models have confirmed that the CPIP@EV–CM combined with US has better ROS production, tumor cell killing, and antimetastasis abilities. The heterogenic fusion membrane strategy and ultrasound-augmented nanoplatform present exciting prospects for designing tumor-immunogenic, self-adjuvant, and expandable vaccines, providing new ideas for exploring new melanoma immunotherapy and antimetastasis strategies, which is expected to be used as a safe and effective treatment in clinical practice.
