Citation: Renwen Zhang, Yixing Zou, Aihua Liao, Jing Luo. Therapeutic improvement of adenomyosis by supramolecular cells-based macrophage membrane-encapsulated dydrogesterone nanoparticles via targeted drug delivery and inhibition of inflammation in the uterus[J]. Chinese Chemical Letters, ;2026, 37(8): 111758. doi: 10.1016/j.cclet.2025.111758 shu

Therapeutic improvement of adenomyosis by supramolecular cells-based macrophage membrane-encapsulated dydrogesterone nanoparticles via targeted drug delivery and inhibition of inflammation in the uterus

Institute of Reproductive Health, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

aihua_liao@hust.edu.cn

luojing117@hust.edu.cn

Received Date: 27 May 2025
Revised Date: 25 August 2025
Accepted Date: 27 August 2025
Available Online: 28 August 2025

Figures(4)

Adenomyosis remains a poorly understood condition characterized by the limited efficacy of current pharmacotherapy. Traditional treatments using dydrogesterone (DG) for adenomyosis often yield suboptimal outcomes due to poor targeting and susceptibility to immune rejection. Therefore, there is an urgent need to identify an effective approach to enhancing the therapeutic efficacy of DG. Given the enrichment of macrophages in the uterus associated with adenomyosis, this study sought to develop a supramolecular cell-based macrophage membrane-encapsulated DG nanoparticle (MM-DG-NP) delivery system for targeted drug delivery and effective treatment of adenomyosis. The MM-DG-NP system leverages a multifaceted therapeutic mechanism by evading phagocytic clearance and enhancing targeted drug delivery efficacy. The supramolecular cell framework, constructed through dynamic non-covalent interactions, provides structural stability and biofunctional adaptability to the MM-DG-NP system, enabling precise homing to uterine macrophage-rich pathological sites. The MM-DG-NP system demonstrated therapeutic efficacy superior to that of traditional DG therapy in murine models, characterized by a pronounced reduction in endometrial invasion depth within the myometrium; effective inhibition of epithelial–mesenchymal transition (EMT) progression in the glandular epithelium; significant attenuation of local inflammatory cytokine release in the uterus, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ); and notable alleviation of pain responses. These results highlight the critical role of supramolecular cell engineering in enhancing the biocompatibility and targeting precision of nanomedicines. MM-DG-NPs thus represent a promising strategy for overcoming current pharmacotherapeutic limitations in adenomyosis, warranting further investigation to explore their potential clinical translation.
- Adenomyosis,
- Supramolecular cells,
- Macrophage membrane,
- Epithelial-mesenchymal transition,
- Anti-inflammatory,
- Therapeutic efficacy
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