Macrophage Anchoring Nanomedicine to Replace Steroids for Intra-articular Injection

巨噬细胞锚定纳米药物替代类固醇用于关节内注射

• 批准号: 10574148
• 负责人: Li Jin
• 金额: $ 17.77万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10574148
• 关键词: Address; Adult; Affect; Animals; Anti-Inflammatory Agents; Antiinflammatory Effect; Arthritis; Binding; Cartilage; Cartilage Matrix; Cell membrane; Charge; Chondrocytes; Confocal Microscopy; Degenerative polyarthritis; Disease; Dose; Drug or chemical Tissue Distribution; Drug usage; Electrostatics; Evaluation; FPR1 gene; Free Radical Scavenging; Fullerenes; Goals; Growth Factor; Harvest; Health Care Costs; Histology; Human; Hyaluronic Acid; Infiltration; Inflammation; Inflammation Mediators; Inflammatory; Injections; Injury; Interleukin-1 beta; Intra-Articular Injections; Joints; Knee; Knee Osteoarthritis; Knee joint; Macrophage; Measures; Mechanics; Medial meniscus structure; Mediator; Modality; Modeling; Monitor; Mus; Musculoskeletal Diseases; Neuropeptides; Nociception; Outcomes Research; Pain; Pathogenesis; Pathology; Penetration; Peptides; Permeability; Persons; Pharmaceutical Preparations; Phenotype; Property; Research; Spinal Ganglia; Steroids; Surface; Symptoms; Synovial Membrane; Therapeutic Effect; Time; Tissue Harvesting; Tissues; Translations; Treatment Efficacy; cartilage degradation; chondroprotection; clinical translation; clinically relevant; clinically significant; confocal imaging; efficacy evaluation; experimental study; fullerene C60; in vivo; in vivo imaging system; injured; joint destruction; joint inflammation; joint injury; knee pain; microCT; mouse model; multiplex assay; nanomedicine; nanoparticle; nanotechnology platform; novel; prevent; receptor; regenerative; synthetic peptide; therapeutic target; uptake

Osteoarthritis (OA) is the most common form of arthritis, affecting more than 32.5 million of US adults, with an associated healthcare cost at more than $185 billion annually. Current treatments for osteoarthritis address symptoms with limited disease-modifying potential. Inflammation is the key mediator of joint OA, making it the key target for osteoarthritis treatment. However, available anti-inflammatory drugs, such as steroids, are rapidly cleared from the joint. Fullerenes (C60) possess potent anti-inflammatory effects and are intrinsically superior to steroids and other molecules due to their long-lasting activity and cell membrane-penetrating capability. We recently developed a nanoplatform cFLFLF-C60 capable of suppressing inflammation and targeting macrophages, potentiating sustained joint retention and therapeutic effects. The goal of this project is to determine the therapeutic efficacy of the nanoplatform on OA and associated pain. Aim 1 will evaluate the efficacy of cFLFLF-C60 in human explant models of inflammatory OA. It will establish whether cFLFLF-C60 inhibits cartilage degradation and inflammation in human joint explants. Aim 2 will determine the sustained effects of treating OA and associated pain in a mouse model. It will elucidate the efficacy and time window of cFLFLF-C60 to modify cartilage degeneration and pain. This project represents a new and distinct direction for the field because it addresses the underlying pathogenesis of OA and sustained joint delivery.

骨关节炎(OA)是最常见的关节炎形式，影响着超过3250万美国成年人， 相关的医疗成本每年超过1850亿美元。目前骨性关节炎的治疗方法 修改疾病的潜力有限的症状。炎症是关节骨性关节炎的关键介质，使其成为 骨性关节炎治疗的关键靶点。然而，现有的抗炎药，如类固醇，正在迅速 从关节中清理出来。富勒烯(C60)具有强大的抗炎作用，本质上优于 类固醇和其他分子由于其持久的活性和穿透细胞膜的能力。我们 最近开发了一种能够抑制炎症和靶向的纳米平台cFLFLF-C60 巨噬细胞，增强持续关节滞留和治疗效果。这个项目的目标是 确定纳米平台对骨性关节炎及相关疼痛的治疗效果。目标1将评估 CFLFLF-C60在人类炎症性骨关节炎外植体模型中的疗效。它将确定cFLFLF-C60是否抑制 人关节移植中软骨的降解和炎症。目标2将确定 在小鼠模型中治疗骨性关节炎及相关疼痛。它将阐明cFLFLF-C60的疗效和时间窗口 改善软骨退变和疼痛。这个项目代表了该领域的一个新的和独特的方向 因为它解决了骨性关节炎和持续联合分娩的潜在发病机制。