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Cited by 68Immunotherapy and Immune ResponsesNanoplatforms for cancer theranosticsCancer Immunotherapy and Biomarkers

Zinc‐Organometallic Framework Vaccine Controlled‐Release Zn 2+ Regulates Tumor Extracellular Matrix Degradation Potentiate Efficacy of Immunotherapy

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Ding, Lin, Liang, Minli, Li, Yuanyuan, Zeng, Mei, Liu, Meiting, Ma, Wei, Chen, Fuming, Li, Chenchen +3 more·2023·Advanced Science
DOI 10.1002/advs.202302967PMC PMC10520680
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Abstract

Abstract Tumor extracellular matrix (ECM) not only forms a physical barrier for T cells infiltration, but also regulates multiple immunosuppressive pathways, which is an important reason for immunotherapy failure. The cyclic guanosine monophosphate‐adenosine monophosphate synthase‐stimulator of interferon genes (cGAS‐STING) pathway plays a key role in activating CD8 + T cells, maintaining CD8 + T cells stemness and enhancing the antitumor effect. Herein, a zinc‐organometallic framework vaccine (ZPM@OVA‐CpG) prepared by self‐assembly, which achieves site‐directed release of Zn 2+ in dendritic cell (DC) lysosomes and tumor microenvironment under acidic conditions, is reported. The vaccine actively targets DC, significantly enhances cGAS‐STING signal, promotes DC maturation and antigen cross‐presentation, and induces strong activation of CD8 + T cells. Meanwhile, the vaccine reaches the tumor site, releasing Zn 2+ , significantly up‐regulates the activity of matrix metalloproteinase‐2, degrades various collagen components of tumor ECM, effectively alleviates immune suppression, and significantly enhances the tumor infiltration and killing of CD8 + T cells. ZPM@OVA‐CpG vaccine not only solves the problem of low antigen delivery efficiency and weak CD8 + T cells activation ability, but also achieves the degradation of tumor ECM via the vaccine for the first time, providing a promising therapeutic platform for the development of efficient novel tumor vaccines.

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  • Metal ion-based loading of proteases effectively addressed the challenge of insufficient enzyme activity in the lesion area due to depletion of metal ions such as zinc ions.

    “Simultaneously, the metal ion–based loading of proteases effectively addressed the challenge of insufficient enzyme activity in the lesion area due to the depletion of metal ions (such as zinc ions) (45, 46).”

    From Matrix mechanical remodeled carrier-free nanosystem for programmable closed-loop reversal of liver fibrosis via STING alkylation (2025) · cites this paper as [45]

    The Introduction (page unavailable) describes MMPs as zinc-dependent proteolytic enzymes and reports reduced zinc concentrations in some tumors. The Results and Discussion (page unavailable) show that zinc delivery increased MMP-2 activity. However, the paper describes a zinc-releasing vaccine that acts on endogenous MMPs, not metal-ion-based loading of proteases, and does not establish that zinc depletion caused insufficient enzyme activity at the lesion. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Ding, L., Liang, M., Li, Y., Zeng, M., Liu, M., Ma, W., Chen, F., Li, C., Reis, R. L., Li, F., & Wang, Y.
Affiliations
  • Southern University of Science and Technology (CN)
  • Clinical Laboratory, Jiaozuo Women's and Child's Hospital Jiaozuo 454001 China
  • Guangdong Medical College (CN)
  • Translational Medicine Collaborative Innovation Center The First Affiliated Hospital (Shenzhen People's Hospital) Southern University of Science and Technology Shenzhen 518020 China
  • Hainan Medical University (CN)
  • 3B's Research Group (PT)
  • The First Affiliated Hospital (Shenzhen People's Hospital) Southern University of Science and Technology Shenzhen 518055 China
Corresponding author
Wang, Yanli
ORCID
Venue
Advanced Science
Publisher
Wiley
Published
2023-07-13
Volume
10
Issue
27
Pages
e2302967-e2302967
ISSN
2198-3844 (ISSN-L)
DOI
10.1002/advs.202302967
PMC
PMC10520680
OpenAlex
W4384119683
Cited by
68
References
4
Citations by year
2026: 17 · 2025: 32 · 2024: 15 · 2023: 4
FWCI
7.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Advanced Science (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
Funders
  • National Natural Science Foundation of China (No. 82001755)
  • National Key Research and Development Program of China (No. 2022YFC2305000)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
cancer vaccines, cGAS-STING pathway, dendritic cell maturation, cross-presentation, CD8+ T cell activation, MMP-2, collagen degradation, tumor immunosuppression, tumor microenvironment
MeSH terms
Delayed-Action Preparations, Dendritic Cells, Humans, Immunotherapy, Neoplasms, Nucleotidyltransferases, Zinc, CD8-Positive T-Lymphocytes, Cancer Vaccines, Matrix Metalloproteinase 2, Tumor Microenvironment

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