Fructose-Coated Nanodiamonds: Promising Platforms for Treatment of Human Breast Cancer.
Fructose-Coated Nanodiamonds: Promising Platforms for Treatment of Human Breast Cancer.
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DOI：
10.1021/acs.biomac.6b00754
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发表时间：
2016-07
影响因子：
6.2
通讯作者：
Jiacheng Zhao;H. Lai;Hongxu Lu;C. Barner‐Kowollik;M. Stenzel;P. Xiao
中科院分区：
文献类型：
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作者：
Jiacheng Zhao;H. Lai;Hongxu Lu;C. Barner‐Kowollik;M. Stenzel;P. Xiao
通过可逆加成-断裂链转移聚合法合成了端羧基功能化的聚（1-O-甲基丙烯酰基-2，3：4，5-二-O-异亚丙基-β-d-吡喃果糖）（Poly（1-O-MAipFru）62），并通过简单的共轭反应将其接枝到胺功能化的纳米金刚石表面。采用红外光谱、热重分析、动态光散射和透射电子显微镜研究了纳米金刚石-聚合物杂化材料ND-Poly（1-O-MAFru）62的性能。在接枝糖基共聚物后，纳米金刚石在水溶液中的分散性得到显著改善。更有趣的是，即使在高浓度（125 μg/mL）下，胺官能化纳米金刚石的细胞毒性在用糖基共聚物修饰后也显著降低。纳米金刚石装载有阿霉素以创建生物活性药物递送载体。阿霉素在pH 5的介质中的释放比在pH 7.4的介质中的释放快。具有阿霉素的纳米金刚石药物递送系统用于在2D和3D模型中治疗乳腺癌细胞。尽管2D细胞培养结果表明，所有纳米金刚石-多柔比星复合物的毒性显著低于游离多柔比星，但在处理8天后，在3D球状体中，包覆有糖基共聚物的纳米金刚石-多柔比星显示出比游离多柔比星更高的细胞毒性。Poly（1-O-MAFru）62-ND-Dox在3D球状体中的增强的细胞毒性可能是由于这些纳米载体的持续药物释放和深度渗透，其起到“特洛伊木马”的作用。在与Poly（1-O-MAFru）62-ND-Dox孵育8天后的大量细胞死亡表明，glycolmonomer包被的纳米金刚石可以是用于乳腺癌治疗的有希望的平台。
Well-defined carboxyl end-functionalized glycopolymer Poly(1-O-methacryloyl-2,3:4,5-di-O-isopropylidene-β-d-fructopyranose) (Poly(1-O-MAipFru)62) has been prepared via reversible addition-fragmentation chain transfer polymerization and grafted onto the surface of amine-functionalized nanodiamonds via a simple conjugation reaction. The properties of the nanodiamond-polymer hybrid materials ND-Poly(1-O-MAFru)62 are investigated using infrared spectroscopy, thermogravimetric analysis, dynamic light scattering, and transmission electron microscopy. The dispersibility of the nanodiamonds in aqueous solutions is significantly improved after the grafting of the glycopolymer. More interestingly, the cytotoxicity of amine-functionalized nanodiamonds is significantly decreased after decoration with the glycopolymer even at a high concentration (125 μg/mL). The nanodiamonds were loaded with doxorubicin to create a bioactive drug delivery carrier. The release of doxorubicin was faster in media of pH 5 than media of pH 7.4. The nanodiamond drug delivery systems with doxorubicin are used to treat breast cancer cells in 2D and 3D models. Although the 2D cell culture results indicate that all nanodiamonds-doxorubicin complexes are significantly less toxic than free doxorubicin, the glycopolymer-coated nanodiamonds-doxorubicin show higher cytotoxicity than free doxorubicin in the 3D spheroids after treatment for 8 days. The enhanced cytotoxicity of Poly(1-O-MAFru)62-ND-Dox in 3D spheroids may result from the sustained drug release and deep penetration of these nanocarriers, which play a role as a "Trojan Horse". The massive cell death after 8-day incubation with Poly(1-O-MAFru)62-ND-Dox demonstrates that glycopolymer-coated nanodiamonds can be promising platforms for breast cancer therapy.