In this study, the novel carrier materials were screened to structure targeting nano-micelles (named 'nano-dandelion') for synchronous delivery of curcumin (Cur) and baicalin (Bai), which could effectively overcome the tumor resistance. Mannose (Man) was found to bind better to CD206 receptors on the surface of tumor-associated macrophages (TAMs), thereby increasing the number of nano-dandelion engulfed by TAMs. Furthermore, oligomeric hyaluronic acid (oHA) was able to target CD44 receptors, resulting in recruitment of a higher number of nano-dandelion to locate and engulf tumor cells. The disulfide bond (S-S) in 3,3'-dithiodipropionic acid (DA) could be broken by the high concentration of glutathione (GSH) in the tumor microenvironment (TME). Based on this, we selected DA to connect hydrophobic fragments (quercetin, Que) and oHA. A reduction-sensitive amphiphilic carrier material, quercetin-dithiodipropionic acid-oligomeric hyaluronic acid-mannose-ferulic acid (Que-S-S-oHA-Man-FA; QHMF) was fabricated and synthesized by 1H NMR. Next, QHMF self-assembled into nano-dandelion, i.e. encapsulated Cur and Bai in water. Critical experimental conditions in the preparation process of nano-dandelion that could affect its final properties were explored. Nano-dandelion with a small particle size (121.0 ± 15 nm) and good normal distribution (PI = 0.129) could easily enter tumor tissue through vascular barrier. In addition, nano-dandelion with a suitable surface potential (-20.33 ± 4.02 mV) could remain stable for a long duration. Furthermore, good cellular penetration and tumor cytotoxicity of nano-dandelion were demonstrated through in vitro cellular studies. Finally, effective antitumor activity and reduced side effects were confirmed through in vivo antitumor experiments in A549 tumor-bearing nude mice.

中文翻译：

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基于靶向肿瘤相关巨噬细胞的低聚透明质酸聚合物的双靶纳米蒲公英的开发，用于非小细胞肺癌的联合治疗。

在这项研究中，将新型载体材料筛选为靶向纳米胶束（称为“纳米蒲公英”）的结构，以同步递送姜黄素（Cur）和黄ical素（Bai），从而可以有效克服肿瘤耐药性。发现甘露糖（Man）与肿瘤相关巨噬细胞（TAMs）表面上的CD206受体更好地结合，从而增加了被TAM吞噬的纳米蒲公英的数量。此外，寡聚透明质酸（oHA）能够靶向CD44受体，从而募集了更多数量的纳米蒲公英来定位和吞噬肿瘤细胞。3,3'-二硫代二丙酸（DA）中的二硫键（SS）可能被肿瘤微环境（TME）中高浓度的谷胱甘肽（GSH）破坏。基于此，我们选择DA连接疏水性片段（槲皮素，Que）和oHA。制备了具有还原敏感性的两亲性载体材料，槲皮素-二硫代二丙酸-低聚透明质酸-甘露糖-阿魏酸（Que-SS-oHA-Man-FA； QHMF），并通过1 H NMR合成。接下来，QHMF自组装成纳米蒲公英，即将Cur和Bai包裹在水中。探索了可能影响其最终性能的纳米蒲公英制备过程中的关键实验条件。具有较小粒径（121.0±15 nm）和良好正态分布（PI = 0.129）的纳米蒲公英可以很容易地通过血管屏障进入肿瘤组织。此外，具有合适表面电势（-20.33±4.02 mV）的纳米蒲公英可以长期保持稳定。此外，通过体外细胞研究证明了纳米蒲公英具有良好的细胞渗透性和肿瘤细胞毒性。最后，