We previously demonstrated that Pleurotus ferulae polysaccharide (PFPS) promoted dendritic cell (DC) maturation through the TLR4 signaling pathway. To improve PFPS activity and bioavailability, gold nanoparticles with PFPS (PFPS-Au NPs) were synthesized. Of note, although the polysaccharide content of PFPS-Au NPs was only one tenth of PFPS, PFPS-Au NPs enhanced the immunostimulatory activities of PFPS in the maturation and function of dendritic cells (DCs) by TLR4 and NLRP3 signaling pathways, evidenced by stronger activation of the down-stream MAPK and NF-κB pathways and NLRP3 inflammasome pathway. More importantly, PFPS-Au NPs enhanced DC migration and murine immunity, particularly in type 1 T-helper cell responses. Moreover, the half-life of PFPS-Au NPs (2.217 ± 0.187 h) was longer than that of PFPS (1.39 ± 0.257 h) in the blood and the distribution of PFPS-Au NPs (19.8 %) in the spleen was significantly increased compared with PFPS (13.3 %), indicating the improved bioavailability in vivo. PFPS-Au NPs as an adjuvant promoted antigen-specific cellular immune responses to an HPV DC-based vaccine, which significantly inhibited the growth of TC-1 tumors in mice. All results suggest that the prepared Au NPs could enhance PFPS-immunostimulatory activity, which will pave the way for PFPS-Au NPs to be applied in clinical trials.
Keywords: Dendritic cell-based vaccine; Gold nanoparticles; Immune responses; Immunostimulatory activity; Pleurotus feruleus polysaccharide.
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