萘普生共轭肽自组装水凝胶治疗骨关节炎。

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-08-11 eCollection Date: 2025-01-01 DOI:10.7150/thno.114781
Lulu Yang, Liang Shao, Puhua Hao, Jiaqi Song, Caiting Meng, Bin Zhu, Hongwen Yu, Wanglin Duan, Xiaohua Fang, Guanying Li, Shichang Liu
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引用次数: 0

摘要

理论基础:骨关节炎(OA)是一种非常普遍的慢性退行性关节疾病,缺乏真正有效的治疗方法。目前的方法受到全身毒性、药物半衰期短和疗效不足的限制。为了解决这个问题,我们开发了一种创新的治疗方法,将非甾体抗炎药(NSAIDs)的药理益处与水凝胶的机械支持和局部递送优势结合起来。方法:设计合成多种萘普生肽缀合物。这些候选物是根据自组装行为、生物相容性和环氧化酶-2 (COX-2)抑制作用筛选的。NpxFFK进行了进一步的研究,包括体外抗炎活性和作用机制的评估。采用足迹分析、显微ct成像、MRI成像、组织染色、免疫组化等方法评价OA大鼠模型的体内治疗效果。通过RNA测序探索其治疗机制。结果:在萘普生肽偶联物NpxFFX (X = R, H, K, E)中,NpxFFK表现出较好的抗炎效果。它自组装成稳定的水凝胶,在关节腔内表现出增强的保留,并提供持续的抗炎作用。体外研究表明,NpxFFK可有效抑制COX-2活性,从而抑制关键炎症因子(IL-1β、IL-6、IL-1和TNF-α)。此外,它使巨噬细胞从M1向M2极化,并促进软骨细胞增殖。体内实验表明,NpxFFK水凝胶显著减轻了OA大鼠的关节降解,优于临床治疗(萘普生治疗或透明质酸治疗),从而验证了其治疗OA的潜力。结论:通过将非甾体抗炎药与自组装肽水凝胶给药平台相结合,我们提出了一种多功能策略,显著改善了当前OA治疗,强调了其在OA管理转化医疗创新方面的前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Self-Assembling Hydrogels of Naproxen-Conjugated Peptides for Osteoarthritis Treatment.

Rationale: Osteoarthritis (OA), a highly prevalent chronic degenerative joint disease, lacks truly effective therapies. Current approaches are limited by systemic toxicity, short drug half-lives, and insufficient efficacy. To address this, we developed an innovative therapeutic approach integrating the pharmacological benefits of nonsteroidal anti-inflammatory drugs (NSAIDs) with the mechanical support and localized delivery advantages of hydrogels. Methods: Various naproxen-peptide conjugates are designed and synthesized. These candidates were screened based on self-assembly behavior, biocompatibility and cyclooxygenase-2 (COX-2) inhibition. NpxFFK underwent further studies including assessment of anti-inflammatory activities and mechanism of action in vitro. In vivo therapeutic efficacy was evaluated in OA rat model using footprinting assay, micro-CT imaging, MRI imaging, histological staining, and immunohistochemistry. The therapeutic mechanism is explored via RNA sequencing. Results: Among naproxen-peptide conjugates NpxFFX (X = R, H, K, E) tested, NpxFFK demonstrated superior anti-inflammatory efficacy. It self-assembled into a stable hydrogel, exhibiting enhanced retention within the joint cavity and providing sustained anti-inflammatory action. In vitro studies revealed that NpxFFK effectively inhibited COX-2 activity, consequently suppressing key inflammatory factors (IL-1β, IL-6, IL-1, and TNF-α). Furthermore, it reprogramed macrophage polarization from M1 toward M2 and promoted chondrocyte proliferation. In vivo experiments demonstrate the NpxFFK hydrogel significantly mitigated articular degradation in OA rats, outperforming clinical treatments (naproxen treatment or hyaluronic acid treatment), thereby validating its therapeutic potential for OA. Conclusions: By integrating NSAID pharmacology with self-assembling peptide hydrogel delivery platform, we present a multifunctional strategy that significantly improves upon current OA treatments, underscoring its promise for translational healthcare innovation in OA management.

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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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