Preparation of Melatonin-Loaded Nanoparticles with Targeting and Sustained Release Function and Their Application in Osteoarthritis.
Preparation of Melatonin-Loaded Nanoparticles with Targeting and Sustained Release Function and Their Application in Osteoarthritis.
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具有靶向和持续释放功能及其在骨关节炎中使用的褪黑激素纳米颗粒的制备。
DOI：
10.3390/ijms24108740
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发表时间：
2023-05-14
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
(1)先天免疫反应与活性氧（ROS）生成的恶性循环是骨关节炎（OA）的重要病理过程。褪黑素因其抗氧化能力可能成为治疗OA的新希望。然而，褪黑素治疗OA的机制尚不完全清楚，关节软骨的生理特性使得褪黑素无法在OA中长期发挥作用。(2)评价褪黑素对骨性关节炎软骨细胞ROS和先天免疫反应系统的影响及体内治疗效果。然后，制备了一种负载褪黑激素的纳米递送系统（MT@PLGA-COLBP）并对其进行了表征。最后，评价MT@PLGA-COLPB在OA小鼠软骨中的行为及治疗效果。(3)褪黑素在体内可通过抑制TLR2/4-MyD88-NFκB信号通路，清除ROS来抑制先天免疫系统的激活，从而改善软骨基质代谢，延缓OA的进展。MT@PLGA-COLBP可以到达软骨内部，完成OA膝关节的积累。同时减少关节内注射次数，提高体内褪黑素的利用率。(4)本工作为骨关节炎的治疗提供了新思路，更新了褪黑素治疗骨关节炎的机制，突出了PLGA@MT-COLBP纳米颗粒在OA预防中的应用前景。
(1) The vicious cycle of innate immune response and reactive oxygen species (ROS) generation is an important pathological process of osteoarthritis (OA). Melatonin may be a new hope for the treatment of OA because of its antioxidant capacity. However, the mechanism of melatonin in the treatment of OA is still not completely clear, and the physiological characteristics of articular cartilage make melatonin unable to play a long-term role in OA. (2) The effects of melatonin on ROS and the innate immune response system in OA chondrocytes and the therapeutic effect in vivo were evaluated. Then, a melatonin-loaded nano-delivery system (MT@PLGA-COLBP) was prepared and characterized. Finally, the behavior of MT@PLGA-COLPB in cartilage and the therapeutic effect in OA mice were evaluated. (3) Melatonin can inhibit the activation of the innate immune system by inhibiting the TLR2/4-MyD88-NFκB signal pathway and scavenging ROS, thus improving cartilage matrix metabolism and delaying the progression of OA in vivo. MT@PLGA-COLBP can reach the interior of cartilage and complete the accumulation in OA knee joints. At the same time, it can reduce the number of intra-articular injections and improve the utilization rate of melatonin in vivo. (4) This work provides a new idea for the treatment of osteoarthritis, updates the mechanism of melatonin in the treatment of osteoarthritis, and highlights the application prospect of PLGA@MT-COLBP nanoparticles in preventing OA.
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