Gas therapy potentiates aggregation-induced emission luminogen-based photoimmunotherapy of poorly immunogenic tumors through cGAS-STING pathway activation

Kaiyuan Wang, Yang Li, Xia Wang, Zhijun Zhang, Liping Cao, Xiaoyuan Fan, Bin Wan, Fengxiang Liu, Xuanbo Zhang, Zhonggui He, Yingtang Zhou (), Dong Wang (), Jin Sun () and Xiaoyuan Chen ()
Additional contact information
Kaiyuan Wang: Shenyang Pharmaceutical University
Yang Li: Chinese Academy of Sciences
Xia Wang: Shenyang Pharmaceutical University
Zhijun Zhang: Shenzhen University
Liping Cao: Shenyang Pharmaceutical University
Xiaoyuan Fan: Shenyang Pharmaceutical University
Bin Wan: Shenyang Pharmaceutical University
Fengxiang Liu: Shenyang Pharmaceutical University
Xuanbo Zhang: Shenyang Pharmaceutical University
Zhonggui He: Shenyang Pharmaceutical University
Yingtang Zhou: Zhejiang Ocean University
Dong Wang: Shenzhen University
Jin Sun: Shenyang Pharmaceutical University
Xiaoyuan Chen: National University of Singapore

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract The immunologically “cold” microenvironment of triple negative breast cancer results in resistance to current immunotherapy. Here, we reveal the immunoadjuvant property of gas therapy with cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation to augment aggregation-induced emission (AIE)-active luminogen (AIEgen)-based photoimmunotherapy. A virus-mimicking hollow mesoporous tetrasulfide-doped organosilica is developed for co-encapsulation of AIEgen and manganese carbonyl to fabricate gas nanoadjuvant. As tetra-sulfide bonds are responsive to intratumoral glutathione, the gas nanoadjuvant achieves tumor-specific drug release, promotes photodynamic therapy, and produces hydrogen sulfide (H2S). Upon near-infrared laser irradiation, the AIEgen-mediated phototherapy triggers the burst of carbon monoxide (CO)/Mn2+. Both H2S and CO can destroy mitochondrial integrity to induce leakage of mitochondrial DNA into the cytoplasm, serving as gas immunoadjuvants to activate cGAS-STING pathway. Meanwhile, Mn2+ can sensitize cGAS to augment STING-mediated type I interferon production. Consequently, the gas nanoadjuvant potentiates photoimmunotherapy of poorly immunogenic breast tumors in female mice.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-38601-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38601-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-38601-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().