A Metal-Phenolic Network-Enabled Nanoadjuvant to Modulate Immune Responses

The presence of hierarchical suppressive pathways in the immune system combined with poor delivery efficiencies of adjuvants and antigens to antigen-presenting cells are major challenges in developing advanced vaccines. The present study reports a nanoadjuvant constructed using aluminosilicate nanoparticles (as particle templates), incorporating cytosine-phosphate-guanosine (CpG) oligonucleotides and small-interfering RNA (siRNA) to counteract immune suppression in antigen-presenting cells. Furthermore, the application of a metal-phenolic network (MPN) coating, which can endow the nanoparticles with protective and bioadhesive properties, is assessed with regard to the stability and immune function of the resulting nanoadjuvant in vitro and in vivo. Combining the adjuvanticity of aluminum and CpG with RNA interference and MPN coating results in a nanoadjuvant that exhibits greater accumulation in lymph nodes and elicits improved maturation of dendritic cells in comparison to a formulation without siRNA or MPN, and with no observable organ toxicity. The incorporation of a model antigen, ovalbumin, within the MPN coating demonstrates the capacity of MPNs to load functional biomolecules as well as the ability of the nanoadjuvant to trigger enhanced antigen-specific responses. The present template-assisted fabrication strategy for engineering nanoadjuvants holds promise in the design of delivery systems for disease prevention, as well as therapeutics. A metal-phenolic network (MPN)-coated nanoadjuvant is constructed using aluminosilicate nanoparticles to deliver an anti-signal transducer and activator of transcription 3 (STAT3) siRNA and immunogenic agents cytosine-phosphate-guanosine, and ovalbumin. The MPN coating improves cell/tissue association in vitro and in vivo, facilitating effective function of anti-STAT3 siRNA to alleviate immunosuppression, leading to enhanced antigen-presenting cell activation and ovalbumin-specific immune responses. image