Microparticles synthesized from itaconate polyesters enable metabolite delivery and elicit immunoregulatory outcomes.

Authors

Amanda N Brocki, Ryan A McIlvaine, Corinne A Martin, Lawrence R Sita, Christopher M Jewell, Senta M Kapnick

Published in

Journal of controlled release : official journal of the Controlled Release Society. Volume 397. Pages 115115. Sep 10, 2026. Epub Jun 17, 2026.

Abstract

Metabolites directly influence immune cell function. Consequently, altering metabolite availability can regulate immunity and represents a window of opportunity for therapeutic manipulation. Itaconate (ITA) - a tricarboxylic acid cycle derivative generated intracellularly - has been shown to exert anti-inflammatory effects in models of autoimmunity. However, efficacy is dependent on systemic, frequent, high-dose treatments due to ITA's poor membrane permeability and rapid clearance from circulation. Thus, there is a need for metabolite delivery strategies that overcome these challenges. Here, we synthesized ITA-based polyesters that enable microparticle (MP) assembly entirely from the polymeric metabolite (pITA). Treatment with biocompatible pITA MPs, which hydrolyze to release unmodified ITA, reduced inflammatory cytokine secretion (e.g., IL-6, IL-1β) by both macrophages and dendritic cells. These data suggest MPs effectively deliver metabolite to the intracellular compartment for immunomodulation in an accessible form. Furthermore, pITA MPs inhibited polarization of inflammatory T cells (T_H17) and promoted regulatory T cells (T_reg), linking the effect of MPs on innate signaling to adaptive immunity. In a preclinical mouse model of multiple sclerosis (MS), pITA MPs reduced circulating serum IL-6 - a cytokine that drives inflammation in several autoimmune diseases. Together, this work advances a biomaterials-based strategy that overcomes hurdles to metabolite delivery and expands opportunities for intervention during autoimmunity and inflammation.

PMID:
42309468
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.

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