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Peer-reviewedCC BY 4.0Molecules

Coordination-Crosslinked Carboxymethyl Chitosan-Mn2+ Hydrogel: Structure–Activity Relationship for In Vitro cGAS-STING Immune Stimulation

  • Yue Yang1
  • Xiaoxin Chen1
  • Shijie Li2
  • Yuncai Xiao2
  • Xianwen Hu1
  1. 1College of Chemistry, Huazhong Agricultural University, Wuhan 430070, China
  2. 2College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
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Abstract

Both carboxymethyl chitosan (CMCS) and Mn2+ can stimulate the cGAS-STING pathway to promote the production of immune factors such as type I interferons (I IFNs), thereby regulating the body’s immune response. In this study, a sustained-release Mn2+-loaded CMCS-Mn hydrogel was designed, and the synergistic effects of CMCS and Mn2+ on innate immunity, as well as factors influencing the immune response, were investigated. The optimal gel formulation was obtained with a CMCS concentration of 1 mg/mL and a MnCl2 concentration of 0.02 mol/L, yielding a gel with a particle size of 472.16 nm, a polydispersity index of 0.35, a Mn2+ content of 1.488 mg/g, and a specific surface area of 4.74 m2/g. The hydrogel forms mainly via coordination interactions between Mn2+ and the amino and carboxyl groups on CMCS molecular chains and exhibits pH-dependent Mn2+ release behavior. Cellular assays demonstrated that the combination of 600 μg/mL CMCS-Mn2+ hydrogel and 5 μg/mL free Mn2+ produced the strongest IFN-β induction. The hydrogel exhibits synergistic immunomodulatory effects of both CMCS and Mn2+; while the amino groups are critical for the immunological activity of CMCS, Mn2+ plays a more prominent role. Partial substitution of Mn2+ by Ca2+ can loosen the cross-linked network and further modulate Mn2+ dissociation from the hydrogel.

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Cite

BibTeXRIS
BibTeX
@article{yang2026coordinationcrosslinked,
  title = {{Coordination-Crosslinked Carboxymethyl Chitosan-Mn2+ Hydrogel: Structure–Activity Relationship for In Vitro cGAS-STING Immune Stimulation}},
  author = {Yue Yang and Xiaoxin Chen and Shijie Li and Yuncai Xiao and Xianwen Hu},
  journal = {Molecules},
  year = {2026},
  month = oct,
  doi = {10.3390/molecules31213891},
  url = {https://www.mdpi.com/1420-3049/31/21/3891},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Coordination-Crosslinked Carboxymethyl Chitosan-Mn2+ Hydrogel: Structure–Activity Relationship for In Vitro cGAS-STING Immune Stimulation
AU  - Yue Yang
AU  - Xiaoxin Chen
AU  - Shijie Li
AU  - Yuncai Xiao
AU  - Xianwen Hu
PY  - 2026
DA  - 2026/10/28
JO  - Molecules
DO  - 10.3390/molecules31213891
UR  - https://www.mdpi.com/1420-3049/31/21/3891
AB  - Both carboxymethyl chitosan (CMCS) and Mn2+ can stimulate the cGAS-STING pathway to promote the production of immune factors such as type I interferons (I IFNs), thereby regulating the body’s immune response. In this study, a sustained-release Mn2+-loaded CMCS-Mn hydrogel was designed, and the synergistic effects of CMCS and Mn2+ on innate immunity, as well as factors influencing the immune response, were investigated. The optimal gel formulation was obtained with a CMCS concentration of 1 mg/mL and a MnCl2 concentration of 0.02 mol/L, yielding a gel with a particle size of 472.16 nm, a polydispersity index of 0.35, a Mn2+ content of 1.488 mg/g, and a specific surface area of 4.74 m2/g. The hydrogel forms mainly via coordination interactions between Mn2+ and the amino and carboxyl groups on CMCS molecular chains and exhibits pH-dependent Mn2+ release behavior. Cellular assays demonstrated that the combination of 600 μg/mL CMCS-Mn2+ hydrogel and 5 μg/mL free Mn2+ produced the strongest IFN-β induction. The hydrogel exhibits synergistic immunomodulatory effects of both CMCS and Mn2+; while the amino groups are critical for the immunological activity of CMCS, Mn2+ plays a more prominent role. Partial substitution of Mn2+ by Ca2+ can loosen the cross-linked network and further modulate Mn2+ dissociation from the hydrogel.
SN  - 1420-3049
ER  -