{"title":"负载α-酮戊二酸的自组装透明质酸纳米粒子对不同阶段骨关节炎的持续治疗效果","authors":"","doi":"10.1016/j.biomaterials.2024.122845","DOIUrl":null,"url":null,"abstract":"<div><div>Osteoarthritis (OA) is a prevalent degenerative disease characterized by irreversible destruction of articular cartilage, for which no current drugs are known to modify its progression. While intra-articular (IA) injections of hyaluronic acid (HA) offer temporary relief, their effectiveness and long-term benefits are debated. Alpha-ketoglutarate (αKG) has potential chondroprotective properties, but its use is limited by a short half-life and poor cartilage-targeting efficiency. Here, we developed self-assembled HA-αKG nanoparticles (NPs) to combine the benefits of both HA and αKG, showing stability, bioavailability, and sustained pH-responsive release in the knee joint. In both early and advanced OA stages in mice, HA, αKG, and HA-αKG NPs could relieve pain, enhance mobility, and reduce cartilage damage, with HA-αKG NPs demonstrating the best efficacy. Mechanistically, αKG not only promotes cartilage matrix synthesis but also inhibits degradation by activating the PERK-ATF4 signaling pathway to reduce endoplasmic reticulum stress (ERS) in chondrocytes. This study highlights the therapeutic potential of HA-αKG NPs for treating various OA stages, with efficient and sustained effects, suggesting rapid clinical adoption and high acceptability among clinicians and patients.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":null,"pages":null},"PeriodicalIF":12.8000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sustained therapeutic effects of self-assembled hyaluronic acid nanoparticles loaded with α-Ketoglutarate in various osteoarthritis stages\",\"authors\":\"\",\"doi\":\"10.1016/j.biomaterials.2024.122845\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Osteoarthritis (OA) is a prevalent degenerative disease characterized by irreversible destruction of articular cartilage, for which no current drugs are known to modify its progression. While intra-articular (IA) injections of hyaluronic acid (HA) offer temporary relief, their effectiveness and long-term benefits are debated. Alpha-ketoglutarate (αKG) has potential chondroprotective properties, but its use is limited by a short half-life and poor cartilage-targeting efficiency. Here, we developed self-assembled HA-αKG nanoparticles (NPs) to combine the benefits of both HA and αKG, showing stability, bioavailability, and sustained pH-responsive release in the knee joint. In both early and advanced OA stages in mice, HA, αKG, and HA-αKG NPs could relieve pain, enhance mobility, and reduce cartilage damage, with HA-αKG NPs demonstrating the best efficacy. Mechanistically, αKG not only promotes cartilage matrix synthesis but also inhibits degradation by activating the PERK-ATF4 signaling pathway to reduce endoplasmic reticulum stress (ERS) in chondrocytes. This study highlights the therapeutic potential of HA-αKG NPs for treating various OA stages, with efficient and sustained effects, suggesting rapid clinical adoption and high acceptability among clinicians and patients.</div></div>\",\"PeriodicalId\":254,\"journal\":{\"name\":\"Biomaterials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":12.8000,\"publicationDate\":\"2024-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomaterials\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S014296122400379X\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, BIOMEDICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomaterials","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S014296122400379X","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
Sustained therapeutic effects of self-assembled hyaluronic acid nanoparticles loaded with α-Ketoglutarate in various osteoarthritis stages
Osteoarthritis (OA) is a prevalent degenerative disease characterized by irreversible destruction of articular cartilage, for which no current drugs are known to modify its progression. While intra-articular (IA) injections of hyaluronic acid (HA) offer temporary relief, their effectiveness and long-term benefits are debated. Alpha-ketoglutarate (αKG) has potential chondroprotective properties, but its use is limited by a short half-life and poor cartilage-targeting efficiency. Here, we developed self-assembled HA-αKG nanoparticles (NPs) to combine the benefits of both HA and αKG, showing stability, bioavailability, and sustained pH-responsive release in the knee joint. In both early and advanced OA stages in mice, HA, αKG, and HA-αKG NPs could relieve pain, enhance mobility, and reduce cartilage damage, with HA-αKG NPs demonstrating the best efficacy. Mechanistically, αKG not only promotes cartilage matrix synthesis but also inhibits degradation by activating the PERK-ATF4 signaling pathway to reduce endoplasmic reticulum stress (ERS) in chondrocytes. This study highlights the therapeutic potential of HA-αKG NPs for treating various OA stages, with efficient and sustained effects, suggesting rapid clinical adoption and high acceptability among clinicians and patients.
期刊介绍:
Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.