Synergistic Glutathione Depletion and STING Activation to Potentiate Dendritic Cell Maturation and Cancer Vaccine Efficacy

Jianping Liu; Ye Zhang; Bowei Yang; Yingbo Jia; Rui-Tian Liu; Lingwen Ding; Zheyu Shen; Xiaoyuan Chen

doi:10.1002/anie.202318530

Synergistic Glutathione Depletion and STING Activation to Potentiate Dendritic Cell Maturation and Cancer Vaccine Efficacy

Angew Chem Int Ed Engl. 2024 Mar 4;63(10):e202318530. doi: 10.1002/anie.202318530. Epub 2024 Jan 23.

Authors

Jianping Liu^{1

2

3}, Ye Zhang^{1

2

4}, Bowei Yang^{1

2}, Yingbo Jia⁵, Rui-Tian Liu⁵, Lingwen Ding^{2

6}, Zheyu Shen³, Xiaoyuan Chen^{1

2

7

8}

Affiliations

¹ Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, 119074, Singapore.
² Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.
³ School of Biomedical Engineering, Southern Medical of University, Guangzhou, Guangdong, 510515, P. R. China.
⁴ CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, Jiangsu, 215123, P. R. China.
⁵ State Key Laboratory of Biochemical Engineering Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, P. R. China.
⁶ Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119074, Singapore.
⁷ Clinical Imaging Research Center, Center for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore.
⁸ Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore.

PMID: 38196070
DOI: 10.1002/anie.202318530

Abstract

Dendritic cell (DC) maturation and antigen presentation are key factors for successful vaccine-based cancer immunotherapy. This study developed manganese-based layered double hydroxide (Mn-LDH) nanoparticles as a self-adjuvanted vaccine carrier that not only promoted DC maturation through synergistically depleting endogenous glutathione (GSH) and activating STING signaling pathway, but also facilitated the delivery of model antigen ovalbumin (OVA) into lymph nodes and subsequent antigen presentation in DCs. Significant therapeutic-prophylactic efficacy of the OVA-loaded Mn-LDH (OVA/Mn-LDH) nanovaccine was determined by the tumor growth inhibition in the mice bearing B16-OVA tumor. Our results showed that the OVA/Mn-LDH nanoparticles could be a potent delivery system for cancer vaccine development without the need of adjuvant. Therefore, the combination of GSH exhaustion and STING pathway activation might be an advisable approach for promoting DC maturation and antigen presentation, finally improving cancer vaccine efficacy.

Keywords: Antigen Delivery; DC Maturation; GSH Depletion; ROS Upregulation; STING Activation.

MeSH terms

Adjuvants, Immunologic / pharmacology
Animals
Cancer Vaccines*
Dendritic Cells
Glutathione
Immunotherapy / methods
Mice
Mice, Inbred C57BL
Nanoparticles*
Neoplasms* / pathology
Ovalbumin
Vaccine Efficacy

Substances

Cancer Vaccines
Adjuvants, Immunologic
Glutathione
Ovalbumin

Abstract

MeSH terms

Substances

Grants and funding