Figure 4. Selective delivery of cGAMP to PV FR-β+ TAMs in Myc-CaP tumors results in STING activation and upregulation of IFNβ. Following the administration of ADT plus LNPs: (A). The proportion of cells in PV and non-PV areas bearing LNPs that were F4/80− vs F4/80+. (B) Fluorescently labeled LNPs colocalized with PV FR-β+F4/80+TAMs. (C, D) FR-β+F4/80+TAMs bearing LNPs were only present in PV areas. (E) When LNPs bearing active cGAMP (LNPs(E)) were administered, the expression of active phosphorylated STING (P-STING) could be detected in LNP+FR-β+F4/80+TAMs. This was accompanied by a significant increase in IFNβ detection PV LNP+F4/80+TAMs (ie, in the LNPs(E) group) (E). In this group, IFNβ detection was only detectable in F4/80+TAMs in PV not NPV areas, (F) but often extended beyond LNP+cells, indicating its possible release and uptake by other cells in tumors (G). This did not occur when mice were injected with LNPs bearing inactive cGAMP. (NPV=non-PV). Data are presented as means±SEMs. *p<0.05, **p<0.01, ***p<0.001. Magnification bars=50 µm. ADT, androgen deprivation therapy; LNP, lipid nanoparticle.