Spatio-controlled Sialic Acid Polymer Molecular Patterns for Selective Siglecs Modulation and Cytokine Storm Abrogation
Cytokine storm is a leading cause of mortality in severe infections and adverse responses to adoptive cell therapiesy. Leveraging multivalent sialic acids (SAs) and the specificity of the SA-Siglec (SA-binding immunoglobulin-type lectins) axis to direct immune cell responses openss 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 Molecular-Patterned Sialic Acid Polymers (MPSPs) Sialic Polymer Molecular Patterns (SPMPMPSPs) , a class of synthetic macromolecular immunomodulators engineered with precise control over polymer backbone conformation, pendant SA densityspacing, and branching topology. This molecular pattern recreates the hierarchical By mimicking the multivalency t architectures of natural glycans while exploiting the modularity of polymer chemistry, and to introduce tunablemolecular controlled SA patterning patterns. Super-resolution fluorescence microscopy and single-molecule spectroscopy confirm structure-specific sialic acid patterns promoteat the molecular scale, SPMPs achieve  Siglec-E clustering and high-affinity engagement with Siglec-E, triggering potent inhibitory signaling . The SPMPs robustly and reshape reshaping innate immune cell functions and effectivelyto abrogated cytokine storms. This pattern-encoded macromolecular strategy es establishes a new paradigm for precise immune modulation and offering a framework for materials-based interventions in inflammatory disorders. Overall design: To compare the change of gene expression of RAW264.7 cells after treated by LPS  and sialic polymers