The swarmable magnetic-driven nanorobots for facilitating trans-intestinal mucosal delivery of oral vaccines to enhance mucosal and systemic immune responses

The continuous secretion of mucus by the intestinal mucosa and the intestinal motility combine to limit the absorption of orally administered vaccines. To extend the residence time of vaccines within the gastrointestinal tract and to improve their mucosal transit, we have developed a technology capable of swiftly and actively traversing the intestinal mucus barrier. In this study, we synthesized a biodegradable magnetic driven nanorobot (MNC@CaMn) loaded with antigen and constructed a magnetic driven nanorobot vaccine delivery platform. Under the precise regulation of the magnetic field, the residence time of the vaccines in the intestine was significantly prolonged, and the vaccine exhibited a swarming motility that could rapidly converge and cross the intestinal mucus barrier in a targeted manner, thus greatly facilitating antigen delivery and presentation and significantly activating CD8⁺ T lymphocytes. In addition, the rough surface of the nanorobot ensured stable antigen loading, while the Mn²⁺ in the particles was able to stimulate efficient mucosal and systemic immune responses due to its excellent adjuvant effect. The magnetic driven nanorobot vaccine delivery system constructed in this study provides a new strategy for the development of efficient oral and mucosal vaccines.