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首页> 外文期刊>Biomaterials Science >Hyaluronic acid hydrophilic surface rehabilitating curcumin nanocrystals for targeted breast cancer treatment with prolonged biodistribution
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Hyaluronic acid hydrophilic surface rehabilitating curcumin nanocrystals for targeted breast cancer treatment with prolonged biodistribution

机译：透明质酸亲水表面恢复姜黄素纳米晶体用于靶向乳腺癌的延长生物分布

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摘要

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.
机译：由于其高治疗效率和低系统性毒性，天然生物活性姜黄素吸引了越来越多的关注作为潜在的抗肿瘤药物。虽然无载载体的纳米晶体技术的出现可以改善溶解度并保证姜黄素，无法控制的药物释放和快速全身代谢的高药物负载是妨碍其在癌症治疗中的进一步应用的明确障碍。这里，透明质酸（HA）改性在姜黄素纳米晶体（Cur-NC）的表面上进行，得到表面重整的亲水性HA @ Cur-NCS，其表现出延长的生物分布。除此之外，HA @ Cur-NC显示过表达MDA-MB-231细胞的CD44中增强的细胞内摄取，但是当用HA预处理时降低摄取。通过流式细胞术证实的凋亡效应表明HA @ Cur-NC可以对MDA-MB-231细胞进行高抗癌活性。在体内药代动力学研究表明，在正常大鼠静脉施用HA @ Cur-NC后，Cur的T（1/2）和平均停留时间（MRT）显着延长。此外，HA @ Cur-NC与游离药物和Cur-NC相比，鼠4T1原位乳腺癌模型中展示了鼠4T1原位乳腺癌模型的优异抗癌效果。总体而言，这些结果表明HA @ Cur-NC作为用于乳腺癌疗法的合适配方的潜力。

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  • 来源
    《Biomaterials Science》 |2020年第1期|共11页
  • 作者

    Ji Peng; Wang Le; Chen Yiwei; Wang Siqi; Wu Zhenghong; Qi Xiaole;

  • 作者单位

    China Pharmaceut Univ Key Lab Modern Chinese Med Nanjing 210009 Peoples R China;

    China Pharmaceut Univ Key Lab Modern Chinese Med Nanjing 210009 Peoples R China;

    China Pharmaceut Univ Key Lab Modern Chinese Med Nanjing 210009 Peoples R China;

    China Pharmaceut Univ Key Lab Modern Chinese Med Nanjing 210009 Peoples R China;

    China Pharmaceut Univ Key Lab Modern Chinese Med Nanjing 210009 Peoples R China;

    China Pharmaceut Univ Key Lab Modern Chinese Med Nanjing 210009 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
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