Polymer-based paclitaxel (PTX) conjugates have demonstrated application potentials to improve the water solubility and enhance the efficiency of drug delivery. In this study, a novel HA-based drug conjugate, HA-6-PTX, was designed and successfully synthesized by chemically grafting PTX to the C-6 position of N-acetyl-d-glucosamine (GlcNAc) of hyaluronic acid (HA) using hexanediamine as the linker. Leaving the carboxylate of HA chain unaffected, the conjugate with drug loading as high as 21.8% showed an excellent water solubility of 168 mg/mL and exhibited increased drug release in the presence of hyaluronidase. Compared to free PTX, HA-6-PTX demonstrated increased cytotoxicity and enhanced apoptosis-inducing effect against HepG2 and A549 cells due to the increased celluar uptake of drug via HA-receptor mediated endocytosis. It was concluded that the HA-6-PTX conjugate could be potentially utilized for further exploration as targeted drug delivery to enhance antitumor efficacy.

中文翻译：

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紫杉醇与C-6己二胺修饰的透明质酸结合，用于靶向药物递送，以增强抗肿瘤功效

基于聚合物的紫杉醇（PTX）偶联物已显示出改善水溶解度和增强药物输送效率的应用潜力。在这项研究中，设计了一种新型的基于HA的药物偶联物HA-6-PTX，并通过将PTX化学接枝到N-乙酰基-d的C-6位置成功合成了-使用己二胺作为连接体的透明质酸（HA）的-葡糖胺（GlcNAc）。HA链的羧酸盐不受影响，载药量高达21.8％的缀合物显示出168 mg / mL的优异水溶性，并在透明质酸酶存在下表现出增加的药物释放。与游离PTX相比，由于通过HA受体介导的内吞作用增加了细胞对药物的摄取，HA-6-PTX表现出增强的针对HepG2和A549细胞的细胞毒性和增强的细胞凋亡诱导作用。结论是，HA-6-PTX偶联物可作为靶向药物递送以增强抗肿瘤功效而潜在地用于进一步探索。