Molecular design of phosphatidylserine-inspired polymers for efficient anti-inflammatory therapy via enhanced interaction with Tim-4

Kosuke Sato; Ahmed Nabil; Komol Kanta Sharker; Kouichi Shiraishi; Mitsuhiro Ebara

doi:10.1038/s41428-025-01140-7

論文 Molecular design of phosphatidylserine-inspired polymers for efficient anti-inflammatory therapy via enhanced interaction with Tim-4

Kosuke Sato (National Institute for Materials Science) ; Ahmed Nabil ; Komol Kanta Sharker ; Kouichi Shiraishi ; Mitsuhiro Ebara (National Institute for Materials Science)

Download file (1.19MB)
Download as zip (801KB)

コレクション

引用

Kosuke Sato, Ahmed Nabil, Komol Kanta Sharker, Kouichi Shiraishi, Mitsuhiro Ebara. Molecular design of phosphatidylserine-inspired polymers for efficient anti-inflammatory therapy via enhanced interaction with Tim-4. Polymer Journal. 2026, (), 407-415. https://doi.org/10.1038/s41428-025-01140-7

(BibTeX)

説明:

(abstract)

This study investigated the interaction between phosphatidylserine (PS)-inspired polymers　and T cell immunoglobulin and mucin-like domain-containing protein 4 (Tim-4) by systematically varying the monomer structure and copolymer composition. A series of alkyl-substituted PS-inspired monomers was synthesized using a modified phosphoramidite method, and well-defined homopolymers and 2-hydroxyethyl methacrylate (HEMA)-containing copolymers were prepared via reversible addition–fragmentation chain-transfer polymerization. Structural analyses using 1H nuclear magnetic resonance and gel permeation chromatography confirmed the successful synthesis with controlled molecular weights. Biolayer interferometry was used to quantify Tim-4 binding, revealing a non-monotonic effect of alkyl substitution, whereas the incorporation of HEMA consistently enhanced Tim-4 binding in a composition-dependent manner. Biological evaluation using RAW-Blue macrophages showed that the homopolymers did not significantly affect interleukin-6 (IL-6) secretion, whereas the copolymers selectively suppressed IL-6 production. Notably, the copolymer containing 50 mol% PS units exhibited the strongest IL-6 suppression, and the HEMA-containing copolymers exhibited anti-inflammatory activity even at lower PS concentrations than the homopolymers. These results demonstrate that copolymer composition critically influences receptor interactions and immune modulation. This study highlights the potential of PS-inspired copolymers as biomaterials that mimic apoptotic cell signals and exert efficient anti-inflammatory effects through an optimized molecular design.

権利情報: