Figure 9.

NANP trafficking and immunostimulation. Green bars indicate levels of serum stability. Black arrows indicate NANP trafficking and localization. Yellow cloud represents the carrier. All NANPs are successfully delivered to cells using L2K and transition from an endosomal compartment to the cytosol. Thickness of black arrows indicates degree of nanoparticle internalization and accumulation. Rc2′F and RcR displayed the highest degree of internalization and DcD displays the lowest degree of internalization. RcD and DcD more rapidly accumulate in the cytosol. We observed RcR, Rc2'F, DcR and Dc2'F display localization in the nuclear fraction. Orange arrows indicate immunostimulation and signaling. Within the endosomal compartment RcR and RcD activate TLR7. Once in the cytosol, RcR, RcD, and Rc2'F activate RIG-I directly. Dc2'F is converted by RNA polymerase III to an RNA intermediate which can activate RIG-I. TLR7 and RIG-I signaling cascades trigger NF-κB and IRF activation and production of IL-6 and IFN-β. Font size indicates the degree of NF-κB and IRF activation or the degree of IL-6 and IFN-β production. Created with BioRender.com