2. Academic Validation
  3. Intermetallic nanoassemblies potentiate systemic STING activation

Intermetallic nanoassemblies potentiate systemic STING activation

  • Science. 2026 May 7;392(6798):eadx1893. doi: 10.1126/science.adx1893.
Xingwu Zhou # 1 2,  Xiang Ling # 1 2,  Xiaoqi Sun 1 2,  Ziye Wan 1 2,  Tobias Dwyer 3,  Timothy C Moore 3,  Quguang Li 1 2,  Hannah E Dobson 1 2,  Qi Wu 1 2,  Xiangbo Kong 4,  Fang Xie 1 2,  Xinran An 1 2,  Jingyao Gan 1 2,  Kaikai Wang 1 2,  Young Seok Cho 1 2,  Wang Gong 5,  Katherine Dong 1 2,  Jie Zhang 1 2,  Mariko Takahashi 1 2,  Cheng Xu 1 2,  Swetha Kodamasimham 1 2,  Jie Xu 4,  Vilma Yuzbasiyan-Gurkan 6 7,  Steven B Chinn 8,  Anna Schwendeman 1 2,  Sharon C Glotzer 2 3,  Yu Leo Lei 5,  James J Moon 1 2 3 9 10
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.
  • 2 Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
  • 3 Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.
  • 4 Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, University of Michigan Medical School, Ann Arbor, MI, USA.
  • 5 Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • 6 Department of Microbiology, Genetics, and Immunology, Michigan State University, East Lansing, MI, USA.
  • 7 Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI, USA.
  • 8 Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
  • 9 Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
  • 10 Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
  • # Contributed equally.
PMID: 42096576 DOI: 10.1126/science.adx1893
Abstract

Natural systems use metal ions to form ordered structures that regulate biological processes, inspiring the rational design of nanotherapeutics. The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway drives antitumor immunity but has been difficult to activate systemically owing to poor pharmacology and toxicity. Here, we report CRYSTAL, a structurally ordered intermetallic nanoparticle for potent systemic STING activation. CRYSTAL self-assembles from manganese ions intercalated with cyclic dinucleotides, enabling precise structural control. At an ultralow intravenous dose (0.003 milligrams per kilogram), CRYSTAL activated STING in mice, dogs, and nonhuman primates without cytokine release syndrome. CRYSTAL induced robust tumor regression in advanced murine and rabbit models, remodeled immunosuppressive environments, and promoted host STING-dependent CD8+ T cell priming. CRYSTAL activated interferon responses in human head and neck squamous cell carcinoma biopsies, underscoring its translational potential for Cancer Immunotherapy.

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