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基于透明质酸的靶向纳米探针的构建及体外抗肿瘤活性

戚筱羽, 叶雨霏, 陈雪梅, 朱晓南, 张雨婷, 尹健, 王晓丽, 周楠迪

戚筱羽, 叶雨霏, 陈雪梅, 朱晓南, 张雨婷, 尹健, 王晓丽, 周楠迪. 基于透明质酸的靶向纳米探针的构建及体外抗肿瘤活性[J]. 中国药科大学学报, 2022, 53(5): 542-553. DOI: 10.11665/j.issn.1000-5048.20220505
引用本文: 戚筱羽, 叶雨霏, 陈雪梅, 朱晓南, 张雨婷, 尹健, 王晓丽, 周楠迪. 基于透明质酸的靶向纳米探针的构建及体外抗肿瘤活性[J]. 中国药科大学学报, 2022, 53(5): 542-553. DOI: 10.11665/j.issn.1000-5048.20220505
QI Xiaoyu, YE Yufei, CHEN Xuemei, ZHU Xiaonan, ZHANG Yuting, YIN Jian, WANG Xiaoli, ZHOU Nandi. Construction of targeted nanoprobe based on hyaluronic acid and its anti-tumor activity in vitro[J]. Journal of China Pharmaceutical University, 2022, 53(5): 542-553. DOI: 10.11665/j.issn.1000-5048.20220505
Citation: QI Xiaoyu, YE Yufei, CHEN Xuemei, ZHU Xiaonan, ZHANG Yuting, YIN Jian, WANG Xiaoli, ZHOU Nandi. Construction of targeted nanoprobe based on hyaluronic acid and its anti-tumor activity in vitro[J]. Journal of China Pharmaceutical University, 2022, 53(5): 542-553. DOI: 10.11665/j.issn.1000-5048.20220505

基于透明质酸的靶向纳米探针的构建及体外抗肿瘤活性

基金项目: 国家自然科学基金资助项目(No.21877054)

Construction of targeted nanoprobe based on hyaluronic acid and its anti-tumor activity in vitro

Funds: This study was supported by the National Natural Science Foundation of China (No.21877054)
  • 摘要: 以透明质酸(hyaluronic acid,HA)为药物递送载体,依次连接阿霉素(doxorubicin,DOX)、天然吲哚花青素染料IR808和过氧化氢酶(catalase,CAT),最后通过自组装得到具有抗肿瘤和荧光成像作用的纳米探针CAT@HA-DOX-IR808 NPs。利用紫外可见光分光度计、荧光分光光度计以及透射电子显微镜等对其进行表征,然后在溶液和细胞水平开展其荧光成像和抗肿瘤活性研究。实验结果表明:构建的纳米探针CAT@HA-DOX-IR808为均匀的近球形,尺寸约为75 nm。在pH 5.0和透明质酸酶环境中,DOX在前10 h的释放率达到80%以上。激光共聚焦结果显示,在CD44阳性细胞中,该纳米探针组展现出比游离药物组以及阴性细胞组更显著的荧光信号。细胞毒实验中,在CAT@HA-DOX-IR808 NPs + NIR组,只有大约40%的MDA-MB-231细胞在最高浓度的CAT@HA-DOX-IR808 NPs下存活。因此,纳米探针CAT@HA-DOX-IR808具有显著增强的抗肿瘤功效,在乳腺癌的体外成像和治疗中具有广阔的应用前景。
    Abstract: Hyaluronic acid (HA) was used as drug delivery carrier, and the doxorubicin (DOX), IR808 and catalase (CAT) were modified on hyaluronic acid (HA) to form the nano-probe CAT@HA-DOX-IR808 NPs with anti-tumor and fluorescence imaging by self-assembly.It was characterized by UV-Vis spectrophotometer, fluorescence spectrophotometer and transmission electron microscope, and its fluorescence imaging and antitumor activity were studied at solution and cell level.The experimental results showed that CAT@HA-DOX-IR808 NPs displayed a uniform near-spherical morphology with a size of 75 nm approximately.Under the condition of pH 5.0 + hyaluronidase (HAase), the release rate of DOX reached more than 80% in the first 10 hours. In the CD44 positive cells, laser confocal imaging results showed that the group of CAT@HA-DOX-IR808 NPs had more significant fluorescence signals than the group of free drugs and negative cell.In the cytotoxicity test, only about 40% of the MDA-MB-231 cells survived at the highest concentration of CAT@HA-DOX-IR808 NPs of the group of CAT@HA-DOX-IR808 NPs + NIR.Therefore, CAT@HA-DOX-IR808 NPs possess significantly enhanced anti-tumor effect with broad application prospect in the imaging and treatment of breast cancer in vitro.
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出版历程
  • 收稿日期:  2022-04-26
  • 修回日期:  2022-06-26
  • 刊出日期:  2022-10-24

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