Therapeutic dendritic cell vaccines engineered with antigen-biomineralized Bi2S3 nanoparticles for personalized tumor radioimmunotherapy

Abstract Therapeutic vaccines, an exciting development in cancer immunotherapy, share the goal of priming of personalized antigen‐specific T‐cell response by precise antigen presentation of dendritic cells (DCs), but major obstacles include insufficient antigen loading and off‐target to DCs remain to their success. Here, we developed an imageable therapeutic vaccine with whole‐antigen loading and target delivery constructed by ovalbumin (OVA)‐biomineralized Bi2S3 nanoparticles‐pulsed DCs. Relying on the strong X‐ray absorption and fluorescence labeling performance of Bi2S3@OVA nanoparticles, the in vivo spatiotemporal fate of the vaccine (Bi2S3@OVA@DC) can be noninvasively monitored by computed tomography and near‐infrared fluorescence imaging in real time. The Bi2S3@OVA@DC can rapidly and durably accumulate in draining lymph nodes and thus trigger stronger T‐cell responses compared to OVA‐pulsed DCs. Meanwhile, Bi2S3@OVA@DC can further achieve in vivo antitumor effects against OVA‐expressing B16F10 melanoma when combined with fractionated radiotherapy, resulting from the upregulation of cytotoxic CD8+ T cells and restraint of regulatory T cells in the tumor microenvironment, and the systemical secretion of OVA‐specific IgG1/IgG2α antibody. Overall, we successfully fabricated an engineered DC vaccine featured in high whole‐antigen loading capacity that can be precisely delivered to the lymphatic system for visualization, serving as a powerful therapeutic platform for cancer radioimmunotherapy.

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