Injectable Hydrogels Coencapsulating Granulocyte-Macrophage Colony-Stimulating Factor and Ovalbumin Nanoparticles to Enhance Antigen Uptake Efficiency

Abstract

The combination of an antigen and adjuvant has synergistic effects on an immune response. Coadministration of an antigen and a granulocyte-macrophage colony-stimulating factor (GM-CSF) hydrogel delivery system will afford a novel strategy for enhancement of an immune response because of the dual role of the hydrogel as a vaccine carrier with a sustained release and a platform for recruiting dendritic cells (DCs). Herein, an injectable poly(caprolactone)–poly(ethylene glycol)–poly(caprolactone) thermosensitive hydrogel coencapsulating GM-CSF and ovalbumin nanoparticles was developed to enhance antigen uptake efficiency. The GM-CSF released from the hydrogel ensured accumulation of DCs; this effect improved the antigen uptake efficiency with the targeted delivery to antigen-presenting cells. Furthermore, the dual delivery system induced a stronger immune effect, including higher CD8+ T proportion, interferon γ secretion, and a greater cytotoxic T lymphocyte response, which may benefit from the recruitment of DCs, increasing antigen residence time, and the controllable antigen release owing to the combined effect of the hydrogel and nanoparticles. Meanwhile, the real-time antigen delivery process in vivo was revealed by a noninvasive fluorescence imaging method. All of the results indicated that the visible dual delivery system may have a greater potential for the efficient and trackable vaccine delivery.