Advanced Science
·
2026
·
IF 14.1
Cheng Chen,Jiaying Li,Jinjin Ma,Xiaonan Yuan,Yao Xiao,Yang Zhang,Yuan Chen,Hao Jiang,Hui He,Jie Hu,Qianglong Chen,Jinniu Zhang,Bin Li,Yun Zhou,Fengxuan Han,Yong Wang
Osteoarthritis (OA) progression involves cartilage degeneration, inflammation, and pain. Recent evidence suggests that the voltage-gated sodium channel Nav1.7, encoded by Scn9a , links nociceptive signaling with chondrocyte metabolic regulation. Here, we developed an acid-responsive, cartilage-targeted delivery system based on WYRGRL peptide-modified chondroitin sulfate/oxidized hyaluronan composite microspheres loaded with carbamazepine (CBZ), termed CBZ/WCOM, for sustained intra-articular CBZ delivery. In interleukin-1β (IL-1β)–challenged chondrocytes, CBZ/WCOM attenuated inflammatory and catabolic responses, as indicated by reduced Ptgs2 , Mmp13 , and Adamts5 expression, while partially restoring anabolic markers including Col2a1 and Acan . Mechanistically, CBZ/WCOM reduced sodium current density, modulated Na⁺/Ca²⁺ exchanger (NCX)-associated Ca 2 + dynamics, and increased heat shock protein 70 (HSP70) and Midkine secretion, supporting the involvement of Nav1.7-related sodium channel signaling in chondrocyte regulation. In a mouse destabilization of the medial meniscus (DMM) model, intra-articular CBZ/WCOM improved mechanical withdrawal thresholds, reduced pain-related neural remodeling, decreased osteophyte formation, partially preserved joint-space width, improved cartilage matrix phenotype, and ameliorated subchondral bone alterations. By integrating WYRGRL-mediated type II collagen (COL2) targeting with pH-triggered CBZ release, CBZ/WCOM supports lesion-localized drug retention and provides a minimally invasive strategy for local OA therapy.
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DOI
PubMed
高影响因子
Nature Communications
·
2026
·Vol. 17
·期 1
·4573
·
IF 18.1
Zhao Qirui,Xu Tongtong,Du Zuchao,Lu Xiaoqing,Zhang Yan,Peng Linjia,Gao Zixuan,Wang Weicheng,Zhu Binyu,Liu Zhigang,Yang Guangjie,Zhao Hui,Song Zhiming,Lou Qiankun,Li Jiaming,Ren Zhiguang,Yu Zhe,Wang Wei,Liu Yanlei,Liang Hui,de la Fuente Jesus M.,Cui Daxiang
Osteoarthritis (OA) is a common degenerative joint disease with limited disease-modifying therapies. Emerging evidence suggests that epigenetic dysregulation contributes to cartilage degeneration, but effective strategies to selectively target these pathways remain lacking. Here we show that the BRD4/Nav1.7 axis drives inflammatory and metabolic dysfunction in OA. Integrated single-cell and transcriptomic analyses identify BRD4 as a key regulator that enhances Nav1.7 transcription, promoting mitochondrial impairment and catabolic activation in chondrocytes. To therapeutically target this pathway, we develop a biomimetic hydrogel system incorporating chondrocyte membrane-coated nanoparticles for cartilage-specific delivery of a BRD4 proteolysis-targeting chimera (PROTAC), a molecule designed to induce selective protein degradation. This nanoplatform enables efficient intra-articular delivery, immune evasion and targeted retention in cartilage. Treatment suppresses inflammatory responses, restores mitochondrial function and reduces cartilage degeneration and pain behaviors in two mouse models of OA. These findings establish targeted BRD4 degradation as a disease-modifying strategy and provide a precision nanotherapeutic platform for OA.
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DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Xinhe Li,Fan Wang,Xinyu Zhang,Bo Liao,Jindong Tan,Xu He,Wang Han,Xiaoqian Ding,Zijie Wang,Anan Jiang,Chuan Liu,Liang Chen,Dingqun Bai,Xiaoyu Han
Osteoarthritis (OA) is one of the most common causes of chronic pain. However, current OA pain therapies often fail to achieve satisfactory outcomes. To effectively alleviate OA pain, ultrasound-responsive piezoelectric analgesic microspheres, constructed using ultrasound and piezoelectric nanomaterials, were developed. Barium titanate (BaTiO 3 ) piezoelectric nanoparticles modified by rabies virus glycoprotein (RVG) were loaded onto gelatin-methacrylate (GelMA) and hyaluronic acid-methacrylate (HAMA) composite hydrogel microspheres (GA/HA) obtained via microfluidic technology to construct analgesic microspheres (BaTiO 3 -RVG@GA/HA). Under ultrasound, the analgesic microspheres can generate electrical pulses. Pain signal transmission is blocked by modulating the voltage-gated sodium channel (VGSCs) Na v 1.7, thus alleviating OA pain. In vitro studies confirmed that analgesic microspheres can effectively reduce the expression of pain-related molecules. In addition, in vivo research results showed that analgesic microspheres can significantly reduce pain-related behaviors and joint pathological damage in rats, achieving improvements in OA pain and joint injury management.
研究领域:
生物医学工程
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纳米医学
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疼痛研究
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材料科学
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骨科
·
神经科学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）