Dynamic Covalent Dual Prodrug Assemblies for Endometritis Therapy via Inflammation Alleviation, Tissue Repair, and Reproductive Function Restoration

Yuhan Zhao, Haoyue Wu, J. Chen, Ying Wang, Zhiru Su, Lixiang Zhao, Yuqin Wang, Y. C. Xu, Xiaomei Li, Chaoyang Zhou, Xiaojian Yan, Honglin Teng, Yuanfeng Li, Yong Liu, Mingqin Lu, Linqi Shi, Xiaoli Hu
In: ACS Nano · 2026 · vol. 20(5) , pp. 4352–4369 · doi:10.1021/acsnano.5c17909 · PMID:41607116 · W7125925976
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

A dynamic covalent dual prodrug nanoplatform (SFB) integrating spermidine and baicalein effectively alleviates endometritis by scavenging reactive oxygen species, suppressing inflammation, and restoring autophagy, leading to improved tissue repair and reproductive function in a mouse model.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text ⓘ

The paper studied a dynamic covalent dual-prodrug nanoplatform (SFB) for treating endometritis, combining spermidine and baicalein using phenylboronic acid-mediated linkage and reaction-induced self-assembly to form nanoparticles with dual-drug loading exceeding 90%. In mechanistic experiments, SFB scavenged reactive oxygen species, inhibited TLR/MyD88/NF-κB–mediated inflammation, reduced apoptosis, and helped restore autophagy-lysosomal homeostasis, with acidic/oxidative responsive release under inflammatory conditions and favorable stability/biosafety. In a mouse endometritis model, SFB reduced oxidative stress, promoted endometrial tissue repair, improved endometrial receptivity, and rescued reproductive impairments related to embryo implantation and fetal development; the abstract does not state major explicit limitations. This paper is centrally about endometriosis — it targets endometritis rather than endometriosis/adenomyosis, though both involve inflammatory processes in the female reproductive tract.

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Abstract

Endometritis is an inflammatory disorder of the endometrium triggered by microbial infection or immune dysregulation, and current therapies, which are largely single-targeted, fail to coordinate multiple mechanisms. Here, we report a dynamic covalent dual prodrug nanoplatform (termed SFB) that integrates the anti-inflammatory, antiapoptotic, and proautophagic effects of spermidine (SPD) and baicalein (BAI). Using phenylboronic acid-mediated linkage and reaction-induced self-assembly (RISA), SFB formed well-defined nanostructures with an exceptionally high dual-drug encapsulation (exceeding 90%). These assemblies enabled responsive and synchronized release under acidic and oxidative inflammatory microenvironments while exhibiting favorable stability and biosafety. Mechanistic studies revealed that SFB efficiently scavenged reactive oxygen species, suppressed TLR/MyD88/NF-κB-mediated inflammation, inhibited apoptosis, and restored autophagy-lysosomal homeostasis. In a mouse model of endometritis, SFB treatment markedly reduced oxidative stress, promoted tissue repair, improved endometrial receptivity, and rescued reproductive impairments associated with embryo implantation and fetal development. Collectively, SFB represents a multifunctional dynamic covalent nanoplatform that enhances therapeutic efficacy against endometrial inflammation, improves reproductive outcomes, and overcomes key limitations of conventional dual-drug delivery strategies, offering opportunities for multidrug synergistic therapy.
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Dynamic Covalent Dual Prodrug Assemblies for Endometritis Therapy via Inflammation Alleviation, Tissue Repair, and Reproductive Function RestorationClick to copy article linkArticle link copied! - Yuhan ZhaoYuhan ZhaoDepartment of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaZhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Gynecology, Consortium for Infection and Innovation(CII), First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, ChinaMore by Yuhan Zhao - Haoyue WuHaoyue WuState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin 300071, ChinaMore by Haoyue Wu - Jiyang ChenJiyang ChenDepartment of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaMore by Jiyang Chen - Ying WangYing WangZhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Gynecology, Consortium for Infection and Innovation(CII), First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, ChinaMore by Ying Wang - Zhiru SuZhiru SuZhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Gynecology, Consortium for Infection and Innovation(CII), First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, ChinaMore by Zhiru Su - Lixiang Zhao*Lixiang Zhao*Email: [email protected]UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, United KingdomMore by Lixiang Zhao - Yuqin WangYuqin WangState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin 300071, ChinaMore by Yuqin Wang - Yi WuYi WuState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin 300071, ChinaMore by Yi Wu - Xiaomei LiXiaomei LiTranslational Medicine Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaMore by Xiaomei Li - Chaoyang ZhouChaoyang ZhouDepartment of Critical Care Medicine, the People’s Hospital of Yuhuan, Taizhou, Zhejiang 317600, ChinaMore by Chaoyang Zhou - Xiaojian Yan*Xiaojian Yan*Email: [email protected]Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Gynecology, Consortium for Infection and Innovation(CII), First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, ChinaMore by Xiaojian Yan - Honglin Teng*Honglin Teng*Email: [email protected]Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaMore by Honglin Teng - Yuanfeng LiYuanfeng LiTranslational Medicine Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaMore by Yuanfeng Li - Yong Liu*Yong Liu*Email: [email protected]Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Gynecology, Consortium for Infection and Innovation(CII), First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, ChinaState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin 300071, ChinaState Key Laboratory of Advanced Polymer Materials, Sichuan University, Chengdu, 610065 Sichuan, ChinaMore by Yong Liu - Mingqin Lu*Mingqin Lu*Email: [email protected]Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaMore by Mingqin Lu - Linqi ShiLinqi ShiDepartment of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin 300071, ChinaMore by Linqi Shi - Xiaoli Hu*Xiaoli Hu*Email: [email protected]Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Gynecology, Consortium for Infection and Innovation(CII), First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, ChinaMore by Xiaoli Hu Abstract Endometritis is an inflammatory disorder of the endometrium triggered by microbial infection or immune dysregulation, and current therapies, which are largely single-targeted, fail to coordinate multiple mechanisms. Here, we report a dynamic covalent dual prodrug nanoplatform (termed SFB) that integrates the anti-inflammatory, antiapoptotic, and proautophagic effects of spermidine (SPD) and baicalein (BAI). Using phenylboronic acid-mediated linkage and reaction-induced self-assembly (RISA), SFB formed well-defined nanostructures with an exceptionally high dual-drug encapsulation (exceeding 90%). These assemblies enabled responsive and synchronized release under acidic and oxidative inflammatory microenvironments while exhibiting favorable stability and biosafety. Mechanistic studies revealed that SFB efficiently scavenged reactive oxygen species, suppressed TLR/MyD88/NF-κB-mediated inflammation, inhibited apoptosis, and restored autophagy-lysosomal homeostasis. In a mouse model of endometritis, SFB treatment markedly reduced oxidative stress, promoted tissue repair, improved endometrial receptivity, and rescued reproductive impairments associated with embryo implantation and fetal development. Collectively, SFB represents a multifunctional dynamic covalent nanoplatform that enhances therapeutic efficacy against endometrial inflammation, improves reproductive outcomes, and overcomes key limitations of conventional dual-drug delivery strategies, offering opportunities for multidrug synergistic therapy. Cited By This article has not yet been cited by other publications. Article Views Altmetric Citations Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days. Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts. The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. 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