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Cellular Analysis and Chemotherapeutic Potential of a Bi-Functionalized Halloysite Nanotube
Pharmaceutics ( IF 4.9 ) Pub Date : 2020-10-13 , DOI: 10.3390/pharmaceutics12100962
Yangyang Luo , Ahmed Humayun , Teresa A. Murray , Benjamin S. Kemp , Antwine McFarland , Xuan Liu , David K. Mills

The surface of halloysite nanotubes (HNTs) was bifunctionalized with two ligands—folic acid and a fluorochrome. In tandem, this combination should selectively target cancer cells and provide a means for imaging the nanoparticle. Modified bi-functionalized HNTs (bi-HNTs) were then doped with the anti-cancer drug methotrexate. bi-HNTs were characterized and subjected to in vitro tests to assess cellular growth and changes in cellular behavior in three cell lines—colon cancer, osteosarcoma, and a pre-osteoblast cell line (MC3T3-E1). Cell viability, proliferation, and cell uptake efficiency were assessed. The bi-HNTs showed cytocompatibility at a wide range of concentrations. Compared with regular-sized HNTs, reduced HNTs (~6 microns) were taken up by cells in more significant amounts, but increased cytotoxicity lead to apoptosis. Multi-photon images confirmed the intracellular location of bi-HNTs, and the method of cell entry was mainly through caveolae-mediated endocytosis. The bi-HNTs showed a high drug loading efficiency with methotrexate and a prolonged period of release. Most importantly, bi-HNTs were designed as a drug carrier to target cancer cells specifically, and imaging data shows that non-cancerous cells were unaffected after exposure to MTX-doped bi-HNTs. All data provide support for our nanoparticle design as a mechanism to selectively target cancer cells and significantly reduce the side-effects caused by off-targeting of anti-cancer drugs.

中文翻译:

双功能埃洛石纳米管的细胞分析和化学治疗潜力。

埃洛石纳米管(HNT)的表面被两个配体-叶酸和荧光染料双官能化。同时,这种组合应选择性地靶向癌细胞并提供对纳米颗粒成像的手段。然后将修饰的双功能化HNT(bi-HNT)掺入抗癌药甲氨蝶呤。对bi-HNT进行了表征,并进行了体外测试,以评估三种细胞系(结肠癌,骨肉瘤和成骨细胞前体细胞系(MC3T3-E1))中的细胞生长和细胞行为的变化。评估细胞活力,增殖和细胞摄取效率。 bi-HNTs在很宽的浓度范围内都显示出细胞相容性。与常规大小的HNT相比,减少的HNT(〜6微米)被细胞吸收的数量更多,但增加的细胞毒性导致细胞凋亡。多光子图像证实了bi-HNTs在细胞内的定位,细胞进入的方法主要是通过小窝介导的内吞作用。bi-HNTs具有甲氨蝶呤的高载药量,并具有较长的释放时间。最重要的是,bi-HNT被设计为特异性靶向癌细胞的药物载体,并且成像数据显示,非肿瘤细胞在暴露于掺有MTX的bi-HNT之后不受影响。
更新日期:2020-10-13
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