Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Wenzhou key Laboratory of basic science and translational research of radiation oncology, Zhejiang 325027, China.
Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
J Control Release. 2022 Jul;347:237-255. doi: 10.1016/j.jconrel.2022.04.037. Epub 2022 May 12.
Osteoarthritis (OA) is a chronic disease caused by joint inflammation. Its occurrence and development depend on a continuous inflammation environment. The activated M1 macrophages play a critical role in the inflammatory response of OA. Regulating the pro-inflammatory M1 to anti-inflammatory M2 macrophages in the OA articular cavity could be a rational strategy for OA treatment. It has been acknowledged that activated macrophages could proactively capture opsonized nanoparticles in the bloodstream and then accumulate into the reticuloendothelial system (RES) organs. Based on this fact, a trapping strategy is proposed, which transforms a normal nanoparticle into an opsonized attractant to target and regulate macrophage polarization. In this study, the opsonized nanoparticle (IgG/Bb@BRPL) had several key features, including an immunoglobulin IgG (the opsonized layer), an anti-inflammatory agent berberine (Bb), and an oxidative stress-responsive bilirubin grafted polylysine biomaterial (BR-PLL) for drug loading (the inner nanocore). In vitro studies confirmed that IgG/Bb@BRPL prefer to be phagocytosed by M1 macrophage, not M0. And the internalized IgG/Bb@BRPL effectively promoted macrophage polarization toward the M2 phenotype and protected nearby chondrocytes. In vivo studies suggested that IgG/Bb@BRPL significantly enhanced therapeutic outcomes by suppressing inflammation and promoting cartilage repair while not prolonging the retention period compared to non-opsonized counterparts. This proof-of-concept study provided a novel opsonization trapping strategy for OA drug delivery and treatment.
骨关节炎（OA）是一种由关节炎症引起的慢性疾病。其发生和发展取决于持续的炎症环境。激活的 M1 巨噬细胞在 OA 关节腔的炎症反应中起着关键作用。调节 OA 关节腔内的促炎 M1 向抗炎 M2 巨噬细胞可能是 OA 治疗的一种合理策略。人们已经认识到，激活的巨噬细胞可以主动捕获血液中的调理纳米颗粒，然后积累到网状内皮系统（RES）器官中。基于这一事实，提出了一种捕获策略，该策略将正常的纳米颗粒转化为调理吸引剂，以靶向和调节巨噬细胞极化。在这项研究中，调理纳米颗粒（IgG/Bb@BRPL）具有几个关键特征，包括免疫球蛋白 IgG（调理层）、抗炎药小檗碱（Bb）和氧化应激响应性胆红素接枝聚赖氨酸生物材料（BR-PLL）用于药物装载（内纳米核）。体外研究证实，IgG/Bb@BRPL 更喜欢被 M1 巨噬细胞吞噬，而不是 M0。并且内化的 IgG/Bb@BRPL 有效地促进了巨噬细胞向 M2 表型的极化，并保护了附近的软骨细胞。体内研究表明，与非调理对照相比，IgG/Bb@BRPL 通过抑制炎症和促进软骨修复，显著提高了治疗效果，而没有延长保留时间。这项概念验证研究为 OA 药物输送和治疗提供了一种新的调理捕获策略。
