Data from: Intermetallic nanoassemblies potentiate systemic STING activation
Data files
Mar 18, 2026 version files 18.25 MB
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DNA_sequencing_for_human_STING_haplotypes.zip
18.25 MB
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README.md
4.18 KB
Abstract
Natural systems utilize metal ions in structurally ordered architectures to regulate essential biological processes, inspiring the rational design of nanostructures for therapeutic applications. The cGAS-STING pathway, a key mediator of innate immunity, detects cytoplasmic DNA and triggers type I interferon (IFN-I) responses essential for antitumor immunity. However, translating STING activation into effective cancer immunotherapy has been challenging due to poor pharmacological properties and systemic toxicity. Here, we report CRYSTAL (Crystal-like STING-Activating nanoassemblies), a structurally ordered intermetallic nanoparticle platform for potent systemic STING activation. CRYSTAL was synthesized via self-assembly of manganese (Mn2+) ions intercalated with cyclic dinucleotides, wrapped within lipid layers. Computational modeling accurately predicted CRYSTAL’s self-assembly behavior, highlighting its tunability and design precision. At ultra-low doses, intravenous CRYSTAL administration effectively activated STING in mice, dogs, and non-human primates, and CRYSTAL demonstrated remarkable antitumor efficacy in late-stage murine and rabbit tumor models. Mechanistically, CRYSTAL reversed immunosuppressive tumor and spleen microenvironments and triggered robust CD8+ T cell priming in a host STING dependent manner. CRYSTAL also induced IFN-I responses in human head and neck squamous cell carcinoma (HNSCC) biopsies, underscoring its translational potential. These findings establish structurally ordered metallo-nanostructures as a promising strategy for metalloimmunotherapy.
Dataset DOI: 10.5061/dryad.qz612jmw8
Description of the data and file structure
The data was collected for an experimental systemic STING activating agonist investigated in preclinical models. Figures are hosted on Zenodo.
Files and variables
File: Data_respository_Fig._1.png
Description:
This is the independent repeat study data for Main Fig. 3C-F.
Data repository Fig. 1: A, Antitumor efficacy of CRYSTAL after antibody-mediated depletion of various immune cells (anti-CD8 and anti-CD4) in B16F10 tumor-bearing mice. B, C, Antitumor efficacy of CRYSTAL in B16F10 tumor-bearing WT, Ifnar⁻/⁻, Ifngr⁻/⁻ C57BL/6 mice (B) or WT and Rag1⁻/⁻ C57BL/6 mice (C). D, Antitumor efficacy of CRYSTAL in STING WT NOOC1 and STING KO NOOC1 tumor-bearing Sting⁻/⁻ C57BL/6 mice. The data represent the mean ± s.e.m. with n = 4-5 (A-C) and n = 3 (D) biologically independent samples. The data were analyzed by two-way ANOVA with Tukey’s HSD multiple comparison post hoc test for tumor growth curve.
File: Data_respository_Fig._2.png
Description:
This is the independent repeat study data for Main Fig. 4.
Data repository Fig. 2: MMTV-PyMT mice (D80 post birth) were enrolled and received IV injections of 10 µg CDA or CRYSTAL on D0, D5, and D10. Tumors and spleens were collected for immune profiling on D15. A-C, Frequency of major immune cell types among CD45⁺ live cells in the TME (A), frequency of CD3⁺ CD8⁺ T cells among CD45⁺ live cells, effector memory (CD44⁺ CD62L⁻) CD8 T cells, and CD11b⁺ Ly6C⁺ Ly6G⁺ MDSC cells among CD45⁺ live cells in tumor (B). C, UMAP plots of tumor CD45⁺ immune cells among untreated and CRYSTAL groups with expression levels of different phenotypic markers. D, frequency of CD3⁺ CD8⁺ T cells among CD45⁺ live cells, central memory (CD44⁺ CD62L⁺) CD8⁺ T cells, effector memory (CD44⁺ CD62L⁻) CD8+^ T cells, Granzyme B (Granz B⁺) expressing CD8⁺ T cells, M2-like (MHC-IIloCD206hi) and M1-like (MHC-IIhiCD206lo) macrophages in spleen. The data represent the mean ± s.e.m. with n = 5 biologically independent samples. The data were analyzed by unpaired two-sided Student’s t-test.
File: Data_respository_Fig._3.png
Description:
This is the independent repeat study data for Main Fig. 4.
Data repository Fig. 3: A, B, Characterization of CD8⁺ T cells phenotypes in the tumor. A, tSNE plots of concatenated CD8⁺ T cells from untreated and CRYSTAL groups with expression levels of different phenotypic markers in tumor and spleen. B, Frequency of effector like (CXCR3⁺) CD8⁺ T cells. C, D, Characterization of CD8⁺ T cells phenotypes in the spleen. C, UMAP plots of concatenated CD8⁺ T cells from untreated and CRYSTAL groups with expression levels of different phenotypic markers. D, Frequency of effector like (CXCR3⁺) CD8⁺ T cells, stem-like memory Sca1⁺ T cells among CD44⁻ CD62L⁺ CD8⁺ T cells, proliferative (Ki67⁺) CD8⁺ T cells, and terminally differentiated (CX3CR1⁺) CD8⁺ T cells. The data represent the mean ± s.e.m. with n = 4 or 5 biologically independent samples. The data were analyzed by unpaired two-sided Student’s t-test.
File: DNA_sequencing_for_human_STING_haplotypes.zip
Description:
This is the DNA sequencing data for Main Fig. 6D-F. Detailed sample name is listed in Excel sheet "DNAseq sample name". Exon 3, 6, and 7 are sequenced with forward and reverse primers. Both sequencing data are provided.
Code/software
For the file "DNA_sequencing_for_human_STING_haplotypes.zip," SnapGene can be used to view the sequence.
Human subjects data
All human participants provided explicit informed consent for the use and public release of their de-identified data, which were anonymized by removing all direct identifiers, minimizing indirect identifiers, and assigning random study codes with no retained re-identification key.