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Dernière publication 01/01/2026

2-Deoxyglucose dendrimer-enabled niclosamide delivery to FRβ-expressing macropha

Abstract Endometriosis is a chronic, incurable disease. Due to limited efficacy, high recurrence rates, and serious side effects of current...

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    [title] => 2-Deoxyglucose dendrimer-enabled niclosamide delivery to FRβ-expressing macropha
    [paragraph] => 2-Deoxyglucose dendrimer-enabled niclosamide delivery to FRβ-expressing macrophages alleviates endometriosis progression and associated hyperalgesia
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Authors
Anubhav Dhull, Mingxin Shi, Madeleine E. Harvey, Taylor M. Page, Rishi Sharma, Kenneth John Goody, Aqib Iqbal Dar, Nash S. Moawad, Vijay Kumar Sirohi, Paul S. Cooke, Kanako Hayashi, Anjali Sharma

 Lab

Journal
bioRxiv
Abstract
Abstract
 
Endometriosis is a chronic, incurable disease. Due to limited efficacy, high recurrence rates, and serious side effects of current treatments, development of new, targeted, non-hormonal therapies is urgently needed. We previously reported that niclosamide, an FDA-approved anthelmintic drug, attenuates endometriotic lesion growth. We further identified folate receptor-β (FRβ)-positive macrophages as contributors to disease progression. Significantly, niclosamide inhibits FRβ+ macrophages and reduces inflammation, innervation, and angiogenesis. To develop niclosamide as a non-hormonal and selective immune cell-targeted therapy for endometriosis, we engineered a folic acid-conjugated 2-deoxyglucose dendrimer (FA-2DG-D) using click chemistry to enable selective FRβ-mediated uptake. Conjugation of niclosamide to FA-2DG-D yielded a targeted nanotherapeutic (FA-2DG-D-Niclo) with enhanced aqueous solubility, controlled intracellular release, and excellent batch-to-batch reproducibility. In a mouse model of endometriosis, FA-2DG-D demonstrated lesion-specific accumulation and selective internalization by FRβ⁺ macrophages with minimal off-target organ retention. A single intraperitoneal dose of FA-2DG-D-Niclo (25 or 50 mg/kg/bw of niclosamide) significantly reduced FRβ⁺ macrophage burden, suppressed lesion number and volume, and markedly improved endometriosis-associated hyperalgesia at two weeks post-treatment. Together, these findings establish FRβ⁺ macrophages as a potential target in endometriosis and present FA-2DG-D-Niclo as a non-hormonal, macrophage-focused nanomedicine for precise and effective endometriosis treatment.
Graphic Abstract

Keywords/Topics
high recurrence rates; von frey filaments; 2-deoxyglucose dendrimer-enabled niclosamide delivery; frβ-expressing macrophages; endometriosis progression; associated hyperalgesia abstract endometriosis; incurable disease; limited efficacy; serious side effects; current treatments
BIOSEB Instruments Used:
Von Frey Filaments (BIO-VF-M)
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Jeu de 20 filaments basé sur le jeu de monofilaments de Wemmes Weinstein - filament rétractable pour protéger celui-ci et faciliter le transport

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