ArticleJournal of controlled release : official journal of the Controlled Release Society2021
Nanoparticle delivery improves the pharmacokinetic properties of cyclic dinucleotide STING agonists to open a therapeutic window for intravenous administration.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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The trial behind it
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Who cites it
68 citing papers in PubMed, 113 citations in OpenAlex.
- Engineered Peptide Self-Assembled Nanofibers for Enhanced STING Activation: A Promising Nanodelivery Platform for Immunotherapy of Pediatric Solid Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The diversity of STING in regulating immune cell function and its role in liver diseases: from bench to bedside.Cell & bioscience · 2026Review
- Rewiring the immune circuit: programming tumor-draining lymph node immunity with nanotechnology.Journal of nanobiotechnology · 2026Review
- Intermetallic nanoassemblies potentiate systemic STING activation.Science (New York, N.Y.) · 2026Article
- A biomimetic nanodisc system selectively activates type I interferons by nonclassical STING pathway for cancer immunotherapy.Nature communications · 2026Article
- Antitumor Activity of Death Receptor 5-Targeted Camptothecin-Loaded Nanoparticles in Murine Syngeneic Models.Biomacromolecules · 2026Article
- Toward oral nanomaterial-based drug delivery systems for hepatocellular carcinoma therapy: evidence mapping, route-specific validation, and translational challenges.Frontiers in pharmacology · 2026Review
- Targeted drug delivery systems for pancreatic cancer therapy: advances, challenges, and future perspectives.Frontiers in immunology · 2026Review
- The Emerging Role of Nanocarrier-Based Delivery Systems for cGAS-STING Activation in Cancer Immunotherapy.International journal of nanomedicine · 2026Review
- Peptide vaccine formulations with structurally distinct STING agonist drugamers induce discrete, efficacious antitumor responses.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- STING agonists trigger monocyte death via apoptosis, pyroptosis, caspase-8 activation and mitochondrial dysfunction.Cell death discovery · 2025Article
- Potentiating cancer immunotherapies with modular albumin-hitchhiking nanobody-STING agonist conjugates.Nature biomedical engineering · 2025Article
- Article
- STING-Activating Nanoparticles Combined with PD-1/PD-L1 Blockade: A Synergistic Approach in Cancer Immunotherapy.Biomedicines · 2025Review
- Nanocarrier-mediated modulation of cGAS-STING signaling pathway to disrupt tumor microenvironment.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Enhancing radiotherapy-induced anti-tumor immunity via nanoparticle-mediated STING agonist synergy.Molecular cancer · 2025Review
- A Multi-Threshold Micelle Improves Tumor Accumulation and STING Immunotherapy.Journal of the American Chemical Society · 2025Article
- Unveiling the crossroads of STING signaling pathway and metabolic reprogramming: the multifaceted role of the STING in the TME and new prospects in cancer therapies.Cell communication and signaling : CCS · 2025Review
- Unleashing the Potential of Metal Ions in cGAS-STING Activation: Advancing Nanomaterial-Based Tumor Immunotherapy.ACS omega · 2025Review
- Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The stimulator of interferon genes (STING) pathway plays an important role in the immune surveillance of cancer and, accordingly, agonists of STING signaling have recently emerged as promising therapeutics for remodeling of the immunosuppressive tumor microenvironment (TME) and enhancing response rates to immune checkpoint inhibitors. 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP) is the endogenous ligand for STING, but is rapidly metabolized and poorly membrane permeable, restricting its use to intratumoral administration. Nanoencapsulation has been shown to allow for systemic administration of cGAMP and other cyclic dinucleotides (CDN), but little is known about how nanocarriers affect important pharmacological properties that impact the efficacy and safety of CDNs. Using STING-activating nanoparticles (STING-NPs) - a polymersome platform designed to enhance cGAMP delivery - we investigate the pharmacokinetic (PK)-pharmacodynamic (PD) relationships that underlie the ability of intravenously (i.v.) administered STING-NPs to induce STING activation and inhibit tumor growth. First, we demonstrate that nanoencapsulation improves the half-life of encapsulated cGAMP by 40-fold, allowing for sufficient accumulation of cGAMP in tumors and activation of the STING pathway in the TME as assessed by western blot analysis and gene expression profiling. Nanoparticle delivery also changes the biodistribution profile, resulting in increased cGAMP accumulation and STING activation in the liver and spleen, which we identify as dose limiting organs. As a consequence of STING activation in tumors, i.v. administered STING-NPs reprogram the TME towards a more immunogenic antitumor milieu, characterized by an influx of >20-fold more CD4
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.