DNA-affibody nanoparticles for inhibiting breast cancer cells overexpressing HER2
DNA-affibody nanoparticles for inhibiting breast cancer cells overexpressing HER2
复制标题
DNA-亲和体纳米颗粒抑制乳腺癌细胞过度表达 HER2
DOI：
10.1039/c6cc08495h
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发表时间：
2017-01-11
影响因子：
4.9
通讯作者：
Chen, Shengxi
中科院分区：
文献类型：
--
作者：
Zhang, Yanmin;Jiang, Shuoxing;Chen, Shengxi
在这项研究中，我们制备了一种DNA修饰的纳米颗粒，它模仿抗体的能力，特异性地靶向HER2受体。这种纳米颗粒的大小(95 KDa)小于曲妥珠单抗(150 KDa)，对BT474细胞的活性至少是曲妥珠单抗的两倍。这种纳米颗粒结构中的DNA具有两个功能，即作为锚定两个亲和体分子的载体和作为载体以非共价结合多个拷贝的小分子药物用于药物输送。每个DNA纳米颗粒可以与53个阿霉素(DOX)分子结合形成复合体，与阿霉素相比，它对过表达HER2的乳腺癌细胞表现出更强的选择性和抑制作用。正如预期的那样，该纳米颗粒在低水平时对表达HER2的细胞的抑制较小。因此，该纳米颗粒代表了一种高效的抑制癌细胞的药物，该癌细胞过度表达HER2，但对正常细胞毒性较低。
In this study, we have prepared a DNA-affibody nanoparticle which mimics a antibody in its ability to specifically target the HER2 receptor. This nanoparticle has a smaller size ( 95 kDa) than the monoclonal antibody, trastuzumab (150 kDa) and at least two-fold greater activity toward BT474 cells than trastuzumab. The DNA in this nanoparticle structure has two functions, namely as a support to anchor two affibody molecules and as a vehicle to non-covalently bind multiple copies of a small molecule drug for drug delivery. Each DNA-affibody nanoparticle can bind similar to 53 molecules of doxorubicin (DOX) to form a complex, which exhibits greater selectivity toward and inhibition of breast cancer cells overexpressing HER2 than doxorubicin does. As expected, the nanoparticle exhibits lesser inhibition of cells expressing HER2 at a low level. Thus, the nanoparticle represents a highly efficacious agent for inhibiting cancer cells which overexpress HER2, but with low toxicity toward normal cells.