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Nano-STING agonist-decorated microrobots boost innate and adaptive anti-tumor immunity

Nano Research volume 16, pages 9848–9858 (2023)Cite this article

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.

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Acknowledgements

We acknowledge the Dr. Glen Kwon lab for the help with nanoparticle characterization. We also want to thank optical imaging core, small animal facilities, flow cytometry core, and histological core in the University of Wisconsin-Madison for their help with this study. This work was supported by the start-up package from the University of Wisconsin-Madison (to Q. Y. H.).

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Authors and Affiliations

  1. Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, 53705, USA

    Yixin Wang, Zhaoting Li, Yu Chen, Allie Barrett, Fanyi Mo & Quanyin Hu

  2. Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53705, USA

    Yixin Wang, Zhaoting Li, Yu Chen & Quanyin Hu

  3. Wisconsin Center for NanoBioSystems, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, 53705, USA

    Yixin Wang, Zhaoting Li, Yu Chen & Quanyin Hu

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  1. Yixin Wang
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  2. Zhaoting Li
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Correspondence to Quanyin Hu.

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Wang, Y., Li, Z., Chen, Y. et al. Nano-STING agonist-decorated microrobots boost innate and adaptive anti-tumor immunity. Nano Res. 16, 9848–9858 (2023). https://doi.org/10.1007/s12274-023-5737-4

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  • DOI: https://doi.org/10.1007/s12274-023-5737-4

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