ROS-responsive resveratrol-loaded cyclodextrin nanomicelles reduce inflammatory osteolysis.
ROS-responsive resveratrol-loaded cyclodextrin nanomicelles reduce inflammatory osteolysis.
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DOI：
10.1016/j.colsurfb.2022.112819
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发表时间：
2022-09
期刊：
影响因子：
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通讯作者：
X. Fang;Junfeng Hu;Qingyun Hu;Han Li;Zhiqiang Sun;Zhigang Xu;Lu Zhang
中科院分区：
文献类型：
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作者：
X. Fang;Junfeng Hu;Qingyun Hu;Han Li;Zhiqiang Sun;Zhigang Xu;Lu Zhang
炎症性疾病如骨髓炎、脓毒性关节炎和牙周炎中的骨丢失是由过度的骨代谢活性引起的。同时，活性氧（ROS）已被确定为破骨细胞分化的贡献者，ROS清除剂的应用已成为一个有前途的策略，以防止骨丢失。最近，白藜芦醇（RSV），多酚类植物抗毒素，已被证明是通过清除活性氧抑制破骨细胞生成;然而，RSV作为抗氧化剂的应用是有限的，其低的水溶性，结构不稳定，和消除半衰期短。在这项研究中，我们开发了一种基于聚乙二醇化环糊精（CD）的纳米平台（PCP），用于局部递送RSV纳米胶束（RSV-NM）。此外，在RSV-NM中用苯基硼酸酯的聚合物官能化成功地实现了RSV的ROS响应性释放。RSV-NMs在体外能显著抑制抗酒石酸酸性磷酸酶（TRAP）阳性多核细胞的形成和F-actin（丝状肌动蛋白）环的形成。此外，骨细胞标志物基因，包括基质金属蛋白酶-9（MMP-9），活化T细胞核因子1（NFATc 1），TRAP和组织蛋白酶K的mRNA表达，因此下调RSV-NMs的存在下，在体内，RSV-NMs提供了对LPS诱导的骨破坏的保护，如破骨细胞数量减少，骨密度增加，骨吸收面积减少所证明的。综上所述，这些结果表明，我们的ROS响应性RSV-NM可用作治疗炎性骨质溶解的潜在治疗剂。
Bone loss in inflammatory disorders such as osteomyelitis, septic arthritis, and periodontitis is caused by excessive osteoclastic activity. Meanwhile, reactive oxygen species (ROS) have been identified as contributors to osteoclast differentiation, and the application of ROS scavengers has emerged as a promising strategy to protect against bone loss. Recently, resveratrol (RSV), a polyphenolic phytoalexin, has been demonstrated to inhibit osteoclastogenesis by scavenging ROS; however, the application of RSV as an antioxidant is limited by its low water solubility, structural instability, and short elimination half-life. In this study, we developed a PEGylated cyclodextrin (CD)-based nanoplatform (PCP) for local delivery of RSV as nanomicelles (RSV-NMs). In addition, polymer functionalization with phenylboronic acid ester in RSV-NMs successfully achieved ROS-responsive release of RSV. The RSV-NMs in a well-dispersed state possessed good biocompatibility as well as improved solubility and stability compared with RSV compound.In vitro, RSV-NMs significantly inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells and suppressed F-actin (filamentous actin) ring formation. Additionally, the mRNA expressions of osteoclastic marker genes, including matrix metalloprotein-9 (MMP-9), nuclear factor of activated T cells 1 (NFATc1), TRAP, and cathepsin K, were consequently downregulated in the presence of RSV-NMs.In vivo, RSV-NMs provided protection against LPS-induced bone destruction, as evidenced by a decreased number of osteoclasts, increased bone density, and reduced area of bone resorption. Taken together, these results indicate that our ROS-responsive RSV-NMs can be employed as a potential therapeutic agent for the treatment of inflammatory osteolysis.