Spatio-controlled sialic acid polymer molecular patterns for selective Siglecs modulation and cytokine storm abrogation
Abstract
Cytokine storm is a leading cause of mortality in severe infections and adverse responses during adoptive cell therapies. Leveraging multivalent sialic acids (SAs) and the specificity of the SA-Siglecs (SA-binding immunoglobulin-type lectins) axis to direct immune cell responses opens a compelling route to efficiently mitigate cytokine storms. However, the optimal configuration of multivalent SAs to maximize Siglec binding affinity and immune-directing activity has yet to be elucidated. Herein, we report Sialic Acid Polymer Molecular Patterns (SPMPs), a class of synthetic macromolecular immunomodulators engineered with precise control over polymer backbone conformation, pendant SA spacing, and branching topology. This molecular pattern recreates the hierarchical multivalency of natural glycans while exploiting the modularity of polymer chemistry and molecular controlled SA patterns. Super-resolution fluorescence microscopy and single-molecule spectroscopy confirm structure-specific sialic acid patterns promote Siglec-E clustering and high-affinity engagement, triggering potent inhibitory signaling and reshaping innate immune cell functions to abrogate cytokine storms. These pattern-encoded macromolecules establish a new paradigm for precise immune modulation and offer a framework for materials-based interventions in inflammatory disorders.
Authors 16
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University of Science and Technology of China · Chinese Academy of Sciences · Changchun Institute of Applied Chemistry
Affiliation as printed
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China
State Key Laboratory of Polymer Science and Technology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
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Chinese Academy of Sciences · Changchun Institute of Applied Chemistry
Affiliation as printed
Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, China
State Key Laboratory of Polymer Science and Technology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
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University of Science and Technology of China · Chinese Academy of Sciences · Changchun Institute of Applied Chemistry
Affiliation as printed
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China
State Key Laboratory of Polymer Science and Technology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
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University of Science and Technology of China · Chinese Academy of Sciences · Changchun Institute of Applied Chemistry · State Key Laboratory of Electroanalytical Chemistry
Affiliation as printed
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
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University of Science and Technology of China · Chinese Academy of Sciences · Changchun Institute of Applied Chemistry · State Key Laboratory of Electroanalytical Chemistry
Affiliation as printed
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
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Harbin Institute of Technology
Affiliation as printed
Harbin Institute of Technology Zhengzhou Research Institute, Zhengzhou, 450018, China
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University of Science and Technology of China · Chinese Academy of Sciences · Changchun Institute of Applied Chemistry
Affiliation as printed
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China
State Key Laboratory of Polymer Science and Technology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
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University of Science and Technology of China · Chinese Academy of Sciences · Changchun Institute of Applied Chemistry · State Key Laboratory of Electroanalytical Chemistry
Affiliation as printed
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
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Affiliation as printed
Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, Brisbane, 4072, Australia
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Affiliation as printed
Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, Brisbane, 4072, Australia
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Affiliation as printed
Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, Brisbane, 4072, Australia
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Chinese Academy of Sciences · Beijing National Laboratory for Molecular Sciences · Institute of Chemistry
Affiliation as printed
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100089, China
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Affiliation as printed
Division of BioTherapeutics, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, 2333CC, Netherlands
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Chinese Academy of Sciences · Changchun Institute of Applied Chemistry · State Key Laboratory of Electroanalytical Chemistry
Affiliation as printed
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
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University of Science and Technology of China · Chinese Academy of Sciences · Changchun Institute of Applied Chemistry
Affiliation as printed
Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, China
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China
State Key Laboratory of Polymer Science and Technology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
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University of Science and Technology of China · Chinese Academy of Sciences · Changchun Institute of Applied Chemistry
Affiliation as printed
Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, China
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China
State Key Laboratory of Polymer Science and Technology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
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