Design and evaluation of dual CD44 receptor and folate receptor-targeting double-smart pH-response multifunctional nanocarrier
Design and evaluation of dual CD44 receptor and folate receptor-targeting double-smart pH-response multifunctional nanocarrier
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DOI：
10.1007/s11051-017-4076-3
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发表时间：
2017-12-14
影响因子：
2.5
通讯作者：
Zhao, Feng
中科院分区：
文献类型：
--
作者：
Chen, Daquan;Song, Xiaoyan;Zhao, Feng
为了提高姜黄素（Cur）的生物利用度和肿瘤靶向性，本文将透明质酸寡糖结合物FA-oHA-Ace-MGK（folicacid oligosaccharides of hyaluronan-acetal-menthone 1，2-glycerol ketal）作为叶酸受体的靶点，以oHA作为CD 44受体的配体，双pH敏感的Ace-MGK作为疏水基团，以FA作为叶酸受体的靶点。采用傅里叶变换红外光谱（FT-IR）和核磁共振氢谱（H-1-NMR）表征了该智能响应多功能双靶向纳米载体的结构特征。通过自组装将抗癌药物Cur成功地负载到FA-oHA-Ace-MGK胶束中。透射电子显微镜（TEM）的测量结果表明，载Cu胶束为球形，平均粒径为166.3 ± 2.12 nm，Zeta电位为-30.07 mV。在温和的酸性环境下比在pH 7.4下，可以从Cur-FA-oHA-Ace-MGK胶束释放更多的包封的Cur。细胞毒性实验表明，非载药胶束对MCF-7细胞和A549细胞基本无细胞毒性，载药胶束的存活率明显低于同浓度的载药胶束，证明载药胶束能有效抑制肿瘤细胞的生长。体外细胞摄取实验证实了其对CD 44受体和叶酸受体的靶向性。这些结果显示FA-oHA-Ace-MGK作为抗肿瘤药物递送的有效纳米尺寸载体的有希望的潜力。
In this article, in order to enhance the bioavailiability and tumor targeting of curcumin (Cur), the oligosaccharides of hyaluronan conjugates, folic acid-oligosaccharides of hyaluronan-acetal-menthone 1,2-glycerol ketal (FA-oHA-Ace-MGK) carried oHA as a ligand to CD44 receptor, double-pH-sensitive Ace-MGK as hydrophobic moieties, and FA as the target of folate receptor. The structure characteristics of this smart response multifunctional dual-targeting nano-sized carrier was measured by fourier-transform infrared (FT-IR) and nuclear magnetic resonance (H-1-NMR). Cur, an anticancer drug, was successfully loaded in FA-oHA-Ace-MGK micelles by self-assembly. The measurement results of transmission electron microscopy (TEM) presented that the Cur-loaded micelles were spherical in shape with the average size of 166.3 +/- 2.12 nm and zeta potential - 30.07 mV. Much more encapsulated Cur could be released at mildly acidic environments than at pH 7.4, from the Cur-FA-oHA-Ace-MGK micelles. Cytotoxicity assay indicated that non-Cur loaded micelles mostly had no cytotoxicity to MCF-7 cells and A549 cells, and Cur-loaded micelles had significantly lower survival rate than Cur suspension in the same concentration, which proved that the drug-loaded micelles can effectively inhibit tumor cell growth. The targeting of CD44 receptors and folate receptors was proved in vitro cellular uptake assay. These results showed the promising potential of FA-oHA-Ace-MGK as an effective nano-sized carrier for anti-tumor drug delivery.