Due to its high therapeutic efficiency and low systemic toxicity, natural bioactive curcumin has attracted more and more attention as a potential antineoplastic drug. Although the emergence of a carrier-free nanocrystalline technology could improve the solubility and guarantee the high drug loading of curcumin, uncontrollable drug release and fast systemic metabolism are definite obstacles that hinder its further application in cancer treatment. Here, hyaluronic acid (HA) modification was carried out on the surface of curcumin nanocrystals (Cur-NC) to obtain surface reformed hydrophilic HA@Cur-NCs that exhibit prolonged biodistribution. Besides this, HA@Cur-NC shows enhanced intracellular uptake in CD44 overexpressing MDA-MB-231 cells, but reduced uptake when pre-treated with HA. The apoptotic effects, confirmed by flow cytometry, suggest that HA@Cur-NC could achieve high anticancer activity against MDA-MB-231 cells. In vivo pharmacokinetic studies suggest that the t_1/2 and mean residence time (MRT) of Cur are significantly extended after the intravenous administration of HA@Cur-NC in normal rats. Moreover, HA@Cur-NC demonstrated superior anticancer effects in a murine 4T1 orthotopic breast cancer model compared with free drug and Cur-NC. Overall, these results show the potential of HA@Cur-NC as a suitable formula for use in breast cancer therapy.

中文翻译：

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透明质酸亲水性表面修复姜黄素纳米晶体，用于具有延长生物分布的靶向乳腺癌治疗。

由于其高治疗效率和低全身毒性，天然的生物活性姜黄素作为潜在的抗肿瘤药受到越来越多的关注。尽管无载体纳米晶体技术的出现可以提高溶解度并确保姜黄素具有较高的载药量，但是不可控的药物释放和快速的全身代谢仍然是阻碍其在癌症治疗中进一步应用的明确障碍。在这里，对姜黄素纳米晶体（Cur-NC）的表面进行了透明质酸（HA）改性，以获得表面重整的亲水性HA @ Cur-NC，其表现出延长的生物分布。除此之外，HA @ Cur-NC在过表达CD44的MDA-MB-231细胞中显示出增强的细胞内摄取，但是在用HA预处理时摄取减少。通过流式细胞仪确认的凋亡作用，体内药代动力学研究表明，在正常大鼠中静脉内注射HA @ Cur-NC后，Cur的t _1/2和平均停留时间（MRT）显着延长。此外，与游离药物和Cur-NC相比，HA @ Cur-NC在鼠4T1原位乳腺癌模型中显示出优异的抗癌作用。总体而言，这些结果表明，HA @ Cur-NC作为用于乳腺癌治疗的合适配方的潜力。