Nanoparticles with CD44 Targeting and ROS Triggering Properties as Effective in Vivo Antigen Delivery System

Currently, development of subunit vaccine based on recombinant antigens or peptides has gradually become an important alternative option for traditional vaccine. However, induction of potent immune response with desired efficacy remains a major challenge. The nanoparticle-based antigen delivery system has been considered a potential carrier system to improve the efficacy of subunit vaccine. In the present study, we have designed an immune-stimulatory delivery system by conjugating three-armed PLGA to PEG via the peroxalate ester bond which is sensitive to hydrogen peroxide (H₂O₂), a major reactive oxygen species (ROS). Hyaluronic acid (HA), a ligand for CD44 receptors was also modified onto the outer shell of the 3s-PLGA-PEG nanoparticles to promote immune cell uptake. For in vitro and in vivo immune response assessment, a model antigen ovalbumin (OVA) was enclosed within the core of the 3s-PLGA-PEG nanoparticles to form 3s-PLGA-PO-PEG/HA nanoparticles (PHO NPs). Our results showed that the PHO NPs enhanced dendritic cell maturation, antigen uptake, and antigen presentation in vitro, likely due to enhanced lysosomal escape. In vivo experiments further revealed that the PHO nanovaccine robustly promoted OVA-specific antibody production and T cell response accompanied by modest stimulation of memory T cells. In summary, the ROS-responsive PHO NPs with modified HA may be an effective vehicle antigen delivery system to promote antigen-induced immune response.