Related Experiment Video
Updated: May 9, 2026
07:04
Immunostimulatory Agent Evaluation: Lymphoid Tissue Extraction and Injection Route-Dependent Dendritic Cell Activation
Published on: September 16, 2018
Intermetallic nanoassemblies potentiate systemic STING activation
Xingwu Zhou1,2, Xiang Ling1,2, Xiaoqi Sun1,2
1Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.
Science (New York, N.Y.)
|May 7, 2026
Summary
Researchers developed CRYSTAL, an ordered nanoparticle that potently activates the STING pathway for cancer immunotherapy. This novel nanotherapeutic shows promise for systemic treatment with minimal toxicity in preclinical models.
Area of Science:
- Biomedical Engineering
- Immunology
- Nanotechnology
Background:
- Natural systems inspire nanotherapeutics using metal ions for biological regulation.
- The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway is crucial for antitumor immunity.
- Systemic activation of the STING pathway is challenging due to poor pharmacology and toxicity.
Purpose of the Study:
- To develop a structurally ordered intermetallic nanoparticle, CRYSTAL, for potent systemic STING activation.
- To evaluate the safety and efficacy of CRYSTAL in preclinical models and non-human primates.
Main Methods:
- CRYSTAL nanoparticles were self-assembled from manganese ions and cyclic dinucleotides.
- Systemic administration of CRYSTAL at an ultralow intravenous dose (0.003 mg/kg).
- Assessment of STING activation, cytokine release, tumor regression, immune microenvironment remodeling, and T cell priming in various animal models and human biopsies.
Main Results:
- CRYSTAL achieved precise structural control and potent systemic STING activation in mice, dogs, and nonhuman primates.
- No cytokine release syndrome was observed at ultralow doses.
- Robust tumor regression in advanced murine and rabbit models, with STING-dependent CD8+ T cell priming.
- Activation of interferon responses in human head and neck squamous cell carcinoma biopsies.
Conclusions:
- CRYSTAL represents a novel nanotherapeutic for potent systemic STING activation.
- The nanoparticle demonstrates a favorable safety profile and significant therapeutic potential for cancer immunotherapy.
- CRYSTAL's ability to remodel the tumor microenvironment and prime T cell responses highlights its translational promise.
Related Concept Videos
01:30Modified-Release Drug Delivery Systems: Stimuli-Activated
Stimuli-activated drug delivery systems are designed to release drugs in response to specific physical, chemical, or biological stimuli. These systems often utilize hydrogels—three-dimensional, hydrophilic polymer networks capable of swelling in aqueous environments and retaining significant fluid volumes. Upon exposure to particular stimuli, these hydrogels undergo structural transitions that allow the embedded drug to be released. Due to this adaptive behavior, such systems are also called...
02:51Metal-Ligand Bonds
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...