2-Deoxyglucose dendrimer-enabled niclosamide delivery to FRβ-expressing macrophages alleviates endometriosis progression and associated hyperalgesia

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)

Source :

https://www.biorxiv.org/content/10.64898/2026.02.06.704463.abstract

Produits associés

Filaments de Von Frey

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