Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, Dalian Minzu University, Dalian, Liaoning 116600, PR China.
Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, Dalian Minzu University, Dalian, Liaoning 116600, PR China; State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, PR China.
Int J Biol Macromol. 2023 Jul 1;242(Pt 2):124736. doi: 10.1016/j.ijbiomac.2023.124736. Epub 2023 May 5.
Quercetin (QT) is a very effective anticancer drug in combating breast cancer. However, it has several disadvantages such as poor water solubility, low bioavailability and low targeting, which seriously restrict its clinical application. In this work, amphiphilic hyaluronic acid polymers (dHAD) were synthesized by grafting dodecylamine to hyaluronic acid (HA). The dHAD self-assembles with QT to form drug-carrying micelles (dHAD-QT). The dHAD-QT micelles possessed excellent drug-loading capacities (75.9 %) for QT and showed significantly improved CD44 targeting compared with unmodified HA. dHAD-QT micelles exhibited high cytotoxicity and apoptosis-inducing abilities, which were ascribed to the pH-sensitive dHAD-QT micelles accomplishing rapid drug release of QT under low pH condition. Importantly, in vivo experiments showed that dHAD-QT effectively inhibited tumor growth in tumor-bearing mice, with a tumor inhibition rate of 91.8 %. Furthermore, dHAD-QT prolonged the survival time of tumor-bearing mice and reduced the toxicity of the drug to normal tissues. These findings indicate that the designed dHAD-QT micelles have promising potential as efficient nano-drugs for breast cancer treatment.
槲皮素 (QT) 是一种非常有效的抗癌药物，可用于治疗乳腺癌。然而，它存在水溶性差、生物利用度低和靶向性低等缺点，严重限制了其临床应用。在这项工作中，通过将十二胺接枝到透明质酸 (HA) 上合成了两亲性透明质酸聚合物 (dHAD)。dHAD 与 QT 自组装形成载药胶束 (dHAD-QT)。dHAD-QT 胶束对 QT 的载药能力（75.9%）非常高，与未修饰的 HA 相比，具有明显改善的 CD44 靶向性。dHAD-QT 胶束具有高细胞毒性和诱导细胞凋亡的能力，这归因于 pH 敏感的 dHAD-QT 胶束在低 pH 条件下能快速释放 QT。重要的是，体内实验表明，dHAD-QT 能有效抑制荷瘤小鼠的肿瘤生长，肿瘤抑制率为 91.8%。此外，dHAD-QT 延长了荷瘤小鼠的生存时间，并降低了药物对正常组织的毒性。这些发现表明，设计的 dHAD-QT 胶束具有作为治疗乳腺癌的有效纳米药物的巨大潜力。
