Nano-STING agonist-decorated microrobots boost innate and adaptive anti-tumor immunity
Yixin Wang, Zhaoting Li, Yu Chen, Allie Barrett, Fanyi Mo, Quanyin Hu
Abstract
Activating the cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of interferon genes (cGAS/STING) signaling has emerged as a promising anti-tumor strategy due to the important role of the pathway in innate and adaptive immunity, yet the selective delivery of STING agonists to tumors following systemic administration remains challenging. Herein, we develop a nano-STING agonist-decorated microrobot platform to achieve the enhanced anti-tumor effect. Fe ions and the STING agonist 2′3′-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) are co-encapsulated in the mitochondria-targeting nanoparticles (mTNPs), which can trigger the release of mitochondrial DNA (mtDNA) by Fenton reaction-induced mitochondria oxidative damage. The exogenous cGAMP and the endogenous mtDNA can work synergistically to induce potent cGAS/STING signaling activation. Furthermore, we decorate mTNPs onto Salmonella typhimurium VNP20009 (VNP) bacteria to facilitate tumor accumulation and deep penetration. We demonstrate that the systemic administration of this microrobot activates both innate and adaptive immunity, improving the immunotherapeutic efficacy of the STING agonists.