A Magnetically Driven\nBiodegradable Microsphere with\nMass Production Capability for Subunit Vaccine Delivery and Enhanced\nImmunotherapy

Subunit vaccines have emerged as a promising strategy\nin immunotherapy\nfor combating viral infections and cancer. Nevertheless, the clinical\napplication of subunit vaccines is hindered by limitations in antigen\ndelivery efficiency, characterized by rapid clearance and inadequate\ncellular uptake. Here, a novel subunit vaccine delivery system utilizing\novalbumin@magnetic nanoparticles (OVA@MNPs) encapsulated within biodegradable\ngelatin methacryloyl (GelMA) microspheres was proposed to enhance\nthe efficacy of antigen delivery. OVA@MNPs-loaded GelMA microspheres,\ndenoted as OMGMs, can be navigated through magnetic fields to deliver\nsubunit vaccines into the lymphatic system efficiently. Moreover,\nthe biodegradable OMGMs enabled the sustained release of subunit vaccines,\nconcentrating OVA around lymph nodes and enhancing the efficacy of\ninduced immune response. OMGMs were produced through a microfluidic\ndroplet generation technique, enabling mass production. In murine\nmodels, OMGMs successfully accumulated antigens in lymph nodes abundant\nin antigen-presenting cells, leading to enhanced cellular and humoral\nimmunity and pronounced antitumor effects with a single booster immunization.\nIn conclusion, these findings highlight the promise of OMGMs as a\npractical subunit vaccination approach, thus addressing the limitations\nassociated with antigen delivery efficiency and paving the way for\nadvanced immunotherapeutic strategies.