Enhanced Therapeutic Efficacy of Doxorubicin for Breast Cancer Using Chitosan Oligosaccharide-Modified Halloysite Nanotubes
Enhanced Therapeutic Efficacy of Doxorubicin for Breast Cancer Using Chitosan Oligosaccharide-Modified Halloysite Nanotubes
复制标题
使用壳寡糖修饰埃洛石纳米管增强阿霉素对乳腺癌的治疗效果
DOI：
10.1021/acsami.6b09074
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发表时间：
2016-10-12
影响因子：
9.5
通讯作者：
Liu, Mingxian
中科院分区：
文献类型：
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作者：
Yang, Jing;Wu, Yanping;Liu, Mingxian
埃洛石纳米管（HNTs）是一种具有独特中空结构的天然硅铝酸盐，具有高比表面积、生物相容性好、无毒、价格低廉等优点。本研究设计了一种壳寡糖接枝的HNTs（HNTs-g-COS）作为阿霉素（DOX）载体，用于乳腺癌的体内外治疗。首先通过各种方法表征了HNTs-g-COS的结构。HNTs-g-COS表面带正电荷，改善了血液相容性。以受控方式在细胞裂解物中释放的装载DOX的HNTs-g-COS（DOX@HNTs-g-COS）。DOX@HNT5-g-COS对MCF-7细胞的IC 50值为1.17 μ g mL（-1），而游离DOX的IC 50值为2.43 μ g mL（-1）。流式细胞术结果显示DOX@HNTs-g-COS增加了MCF-7细胞的凋亡效应。DOX@HNTs-g-COS诱导的细胞活性氧水平呈剂量依赖性。DOX@HNTs-g-COS可进入MCF-7细胞，引起线粒体损伤，并攻击细胞核。在4 T1荷瘤小鼠中研究DOX@HNTs-g-COS的体内抗肿瘤作用。DOX@HNTs-g-COS的抑瘤率为83.5%，而游离DOX的抑瘤率为46.1%。所有用DOX@HNTs-g-COS处理的小鼠存活超过60天。DOX@HNT5-g-COS心肌细胞破裂较少，无明显全身毒性。因此，合理设计的HNTs纳米化疗药物载体在肿瘤治疗中具有广阔的应用前景。
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 IC50 value of DOX@HNT5-g-COS toward MCF-7 cells was 1.17 mu g mL(-1), while it was 2.43 mu g mL(-1) 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@HNT5-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.