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

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

doi:10.1007/s12274-023-5737-4

Nano Research 2023, 16(7): 9848-9858 https://doi.org/10.1007/s12274-023-5737-4

Research Article | Issue | Published: 31 May 2023

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

Show Author's Information Hide Author's Information Yixin Wang^{¹^,²^,³}, Zhaoting Li^{¹^,²^,³}, Yu Chen^{¹^,²^,³}, Allie Barrett^¹, Fanyi Mo^¹, Quanyin Hu^{¹^,²^,³}(

)

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

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

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

Keywords:

drug delivery, bacteria, Fenton reaction, stimulator of interferon genes (STING), tumor immunotherapy, mitochondrial DNA (mtDNA)

Topics:

Bacteria Cell engineering Controlled drug delivery Drug delivery Nanobiotechnology Targeted drug delivery Tumors

Cite this article:

Wang Y, Li Z, Chen Y, et al. Nano-STING agonist-decorated microrobots boost innate and adaptive anti-tumor immunity. Nano Research, 2023, 16(7): 9848-9858. https://doi.org/10.1007/s12274-023-5737-4

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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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About this article

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

Show Author's information Hide Author's Information Yixin Wang^{¹^,²^,³}, Zhaoting Li^{¹^,²^,³}, Yu Chen^{¹^,²^,³}, Allie Barrett^¹, Fanyi Mo^¹, Quanyin Hu^{¹^,²^,³}(

)

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

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

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

Abstract

Keywords: drug delivery, bacteria, Fenton reaction, stimulator of interferon genes (STING), tumor immunotherapy, mitochondrial DNA (mtDNA)

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Acknowledgements

Publication history

Received: 18 February 2023

Revised: 09 April 2023

Accepted: 13 April 2023

Published: 31 May 2023

Issue date: July 2023

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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.).