Size-controlled immunomodulatory and vaccine adjuvant potentials of self-assembled hyaluronic acid nanoparticles: Activation and recruitment of immune cells.

Immunotherapy has paramount importance in treating chronic immune diseases, and vaccine development. Hyaluronic acid (HA) has been shown to elicit molecular weight-related distinct immune responses. Nonetheless, the particle size-dependent immunomodulatory effects of hyaluronic acid nanoparticles (HA-NPs) remain blurred. Thus, the present study aimed at investigating the effect of polymer configuration and particle size of HA-NPs assembled from HA36K-ODA and HA360k-ODA analogs in modulating macrophage-related immune activities. In the in vitro experiments, HA-NPs of HA36k-ODA analogs garnered significantly enhanced nitrite production with low interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) secretion in macrophages. Furthermore, smaller (< 200 nm) HA36k-ODA NPs activated CD11b+ cells whereas a ∼ 130 nm HA36k-ODA15 NPs preferentially induced CD11c+ cells in vivo, indicating the influence of particle size on the antigen-presenting cells (APCs) recruitment. Interestingly, self-assembled HA36k-ODA15 NPs without ovalbumin (OVA) activated immature dendritic cells (DCs) and augmented their migration toward the lymph nodes (LNs). Notably, HA36k-ODA15-activated macrophages behaved like M1 phenotype macrophages. Overall, our findings garnered valuable insights about the design and application of HA-NPs for modulating the immune responses in nanoscale materials-based immunotherapy.