文献：Intra-articular Administrated Hydrogels of Hyaluronic Acid Hybridized with Triptolide/Gold

Nanoparticles for Targeted Delivery to Rheumatoid Arthritis Combined with Photothermal-chemo Therapy

文献链接：https://www.semanticscholar.org/paper/Intra-articular-Administrated-Hydrogels-of-Acid-for-Li-Liu/019c154560e9ceae7e9d56b37ea5d800bf74a1b9

作者：Chenxi Li ,Rui Liu ,Yurong Song ,Dongjie Zhu,Liuchunyang Yu ,Qingcai Huang,Zhengjia Zhang ,Zeyu Xue,Zhenglai Hua ,Cheng Lu ,Yuanyan Liu

相关产品：RGD

原文摘要：Triptolide (TP) as a disease-modifying anti-rheumatic drug (DMARD) is effective on the treatment of rheumatoid arthritis (RA). To alleviate the toxicity and elevate therapeutic specifi city, hyaluronic acid (HA) hydrogels load RGD-attached gold nanoshell containing TP are synthesized, which can be used for targeted photothermal-chemo therapy, and imaging of RA in vivo. The hydrogels system composed of thiol and tyramine modifi ed HA conjugates has been applied artifi cial tissue models of cartilage for studying drug delivery and release properties. After the degradation of HA chains, heat together with drugs can be delivered to the infl ammatory joints simultaneously due to the near-infrared resonance (NIR) irradiation of Au nanoshell. RA is a chronic infl amed disease, which is characterized by synovial infl ammation of multiple joints, and can be penetrated with NIR light. These intra-articular administrated hybrid hydrogels combined with NIR irradiation can improve clinical arthritic conditions and infl amed joints in collagen-induced arthritis (CIA) mice, which just need a smaller dosage of TP with non-toxicity. Additionally, the TP-Au/HA hybrid hydrogels treatment reduced the invasion and migration of RA fi broblast-like synoviocytes (RA-FLSs) in vitro signifi cantly, through reducing the phosphorylation of mTOR and p70S6K, its substrates, and confi rmed that the mTOR pathway was inhibited.

RGD 即精氨酸 - 甘氨酸 - 天冬氨酸三肽序列，RGD 序列对整合素受体具有很高的亲和力。整合素是一类广泛存在于细胞表面的跨膜受体蛋白，在细胞黏附、迁移、增殖和分化等过程中发挥着重要作用。RGD 序列能够特异性地与整合素受体结合，激活细胞内的信号传导通路，从而影响细胞的行为。TP-Au/HA 是一种具有特定组成和特性的材料。引用的这篇文献就结合两者特性制备了TP-Au/HA杂化水凝胶，具体步骤如下：

图为：TP-Au-RGD纳米颗粒嵌入在水凝胶基质中

TP-Au-RGD纳米颗粒的制备：

采用柠檬酸钠还原法制备了AuNps。将HAuCl4溶液加热至沸腾。然后搅拌溶液，同时在溶液中滴加入柠檬酸钠，保持还原时间。之后，将溶液保持煮沸，直到溶液变成红紫色，转移到fl溶液中。然后，在超声波搅拌下，将柠檬酸钠溶液和HAuCl4溶液加入到TP-PLGA-AuNps中。然后逐滴加入羟胺溶液搅拌，实现超声作用下HAuCl4的还原。将TP-PLGA-Au纳米颗粒从底物中通过超声处理分散到SH-PEG-COOH溶液中，并离心收集。在磁搅拌下，收集的羧酸端TP-PLGA-Au纳米颗粒、环RGD、NHS和EDC在室温下分散在PBS中。在此期间，RGD多肽共价结合到吸附在金纳米壳上的SH-PEG-COOH链的-羧基基团上。离心后收集TP-AuRGD纳米颗粒，丢弃含有未反应的环状RGD的上清液。最后，将得到的TP-Au-RGD纳米颗粒冷冻干燥并保存。

RGD在TP-Au/HA杂化水凝胶制备及表征中的应用：

首先，制备TP-PLGA纳米颗粒。接下来，通过静电相互作用，用AuNps有序修饰得到TP-PLGAAuNps纳米颗粒，在TP-PLGA-AuNps周围减少HAuCl4，在TP-PLGA纳米颗粒[19]外形成金纳米壳。用柠檬酸钠还原和稳定HAuCl4，在煮沸条件下制备了AuNps。将TP-PLGA-Au纳米颗粒通过超声处理分散到SH-PEG-COOH溶液中，离心收集。靶向递送的环RGD肽可以结合Blood vessels生成Blood vessels内皮细胞上表达的Rvβ3。得到的TP-Au-RGD纳米粒子的1H NMR谱。在UV-vis-NIR光谱中，表明Au纳米壳格式形成，纳米颗粒可用于体内NIR吸光度成像和光热Treatment 。

图为：TP-Au/HA混合水凝胶的扫描电镜图像

结论：RGD 序列能够与细胞表面的整合素受体特异性结合，促进细胞在水凝胶表面的黏附。在 TP-Au/HA 杂化水凝胶中引入 RGD，可以使水凝胶具有更好的细胞亲和性，为细胞的生长和增殖提供良好的环境。RGD 具有生物活性，可以调节细胞的行为，如促进细胞增殖、分化和迁移等。将 RGD 引入到 TP-Au/HA 杂化水凝胶中，可以赋予水凝胶一定的生物活性，使其在生物医学领域具有应用前景。通过细胞黏附实验可以评估 RGD 在水凝胶表面的作用效果。将细胞接种在含有 RGD 的 TP-Au/HA 杂化水凝胶上，观察细胞的黏附情况、形态和增殖情况，可以直观地了解 RGD 对细胞黏附性的影响。