Department of Materials Science and Engineering and ‡College of Pharmacy, Jinan University , Guangzhou 510632, China.
ACS Appl Mater Interfaces. 2016 Oct 12;8(40):26578-26590. doi: 10.1021/acsami.6b09074. Epub 2016 Sep 27.
Halloysite nanotubes (HNTs) are natural aluminosilicates with unique hollow lumen structure, also having high specific area, good biocompatibility, nontoxicity, and low price. Here, we designed a chitosan oligosaccharide-grafted HNTs (HNTs-g-COS) as a doxorubicin (DOX) carrier for treating breast cancer both in vitro and in vivo. The structure of HNTs-g-COS was first characterized by various methods. HNTs-g-COS showed positively charged surface and improved hemocompatibility. DOX-loaded HNTs-g-COS (DOX@HNTs-g-COS) released in cell lysate in a controlled manner. The IC value of DOX@HNTs-g-COS toward MCF-7 cells was 1.17 μg mL, while it was 2.43 μg mL for free DOX. DOX@HNTs-g-COS increased the apoptosis effects of MCF-7 cells as shown in flow cytometry results. Also, reactive oxygen species of cells induced by DOX@HNTs-g-COS were drug-dose-dependent. DOX@HNTs-g-COS could enter the MCF-7 cells and induce mitochondrial damage as well as attack the nuclei. The in vivo antitumor effect of DOX@HNTs-g-COS was investigated in 4T1-bearing mice. The tumor-inhibition ratio of DOX@HNTs-g-COS was 83.5%, while it was 46.1% for free DOX. All mice treated with DOX@HNTs-g-COS survived over 60 days. DOX@HNTs-g-COS showed fewer ruptured cardiomyocytes and no obvious systemic toxicity. Therefore, the rational designed HNTs nanocarrier for chemotherapy drug showed promising applications in tumor treatment.
羟硅铝石纳米管（HNTs）是一种具有独特中空腔结构的天然铝硅酸盐，具有比表面积高、生物相容性好、无毒、价格低廉等特点。在这里，我们设计了一种壳聚糖寡糖接枝羟硅铝石纳米管（HNTs-g-COS）作为阿霉素（DOX）载体，用于体外和体内治疗乳腺癌。首先通过各种方法对 HNTs-g-COS 的结构进行了表征。HNTs-g-COS 表现出带正电荷的表面和改善的血液相容性。载 DOX 的 HNTs-g-COS（DOX@HNTs-g-COS）在细胞裂解液中以可控的方式释放。DOX@HNTs-g-COS 对 MCF-7 细胞的 IC 值为 1.17 μg mL，而游离 DOX 为 2.43 μg mL。DOX@HNTs-g-COS 增加了 MCF-7 细胞的凋亡作用，如流式细胞术结果所示。此外，细胞中由 DOX@HNTs-g-COS 诱导的活性氧物种呈药物剂量依赖性。DOX@HNTs-g-COS 可以进入 MCF-7 细胞并诱导线粒体损伤以及攻击细胞核。在 4T1 荷瘤小鼠中研究了 DOX@HNTs-g-COS 的体内抗肿瘤作用。DOX@HNTs-g-COS 的肿瘤抑制率为 83.5%，而游离 DOX 为 46.1%。所有用 DOX@HNTs-g-COS 治疗的小鼠均存活超过 60 天。DOX@HNTs-g-COS 显示出较少的破裂心肌细胞，没有明显的全身毒性。因此，这种用于化疗药物的合理设计的 HNTs 纳米载体在肿瘤治疗中具有广阔的应用前景。
