STING agonist delivery by lipid calcium phosphate nanoparticles enhances immune activation for neuroblastoma

Neuroblastoma (NB) is a common solid tumor in children and infants, the formation regression of which closely linked to tumor-host immune relationship. Stimulator interferon genes (STING) agonists, particularly cyclic dinucleotide (CDN), have promising potential NB therapy by generating innate adaptive stimulation, thus leading control. CDN delivery vivo challenging due negative charge, hydrophilicity, susceptibility degradation phosphodiesterase, hinders effectiveness CDN. Thus, our study proposed four methods load into liposomes, using 2′,3′-cGAMP as model drug. Lipid nanoparticles were prepared, followed physicochemical characterization. Subsequently, cellular inhibition stimulation investigated. As result, lipid calcium phosphate (LCP-NPs) possessed highest encapsulation efficiency among preparation methods, with diameter 82.57±3.72 nm. LCP-NPs maintained size stability under refrigeration conditions at 4°C within 48 h. The surface liposome was positively charged. Compared free cGAMP, resulted slower release, enhanced cytotoxicity against cells, greater activation cGAS-STING pathway, increased expression factors. Taken together, these findings clearly demonstrated liposomal system for cGAMP provided strategy treatment NB.