Biodegradable STING agonist nanoparticles for enhanced cancer immunotherapy

While cyclic dinucleotides (CDNs; STING agonists) are potent IFN inducing agents, these adjuvants have a narrow therapeutic window partly due to their inability to efficiently bypass the cellular membrane. The net negative charge of CDNs limits their cytosolic bioavailability and interaction with the cytosolic protein STING, necessitating micromolar extracellular concentrations for effective activation. Here, we demonstrate the utilization of biodegradable, cationic polymeric nanoparticles for cytosolic delivery of CDNs to professional antigen presenting cells for log-fold improved adjuvant activity in vitro and in vivo.321