基于碳点多功能纳米载药体系的制备及pH响应释药性能研究

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采用一步微波法成功制备了表面带氨基的荧光纳米碳点CDots,并通过酰胺化反应将靶向基团叶酸接枝到碳点表面,成功获得中间产物CDots-FA.在此基础上,通过已合成四臂端酰肼基化合物2与抗肿瘤药物阿霉素(DOX)连接,实现在碳点表面的阿霉素药物分子的化学键合,最终获得多功能纳米载药体系DOX-CDots-FA.利用原子力显微镜(AFM)、高分辨透射电镜(HR-TEM)和荧光光谱仪对荧光纳米碳点CDots的性能进行表征,并通过核磁共振、紫外-可见吸收光谱对DOX-CDots-FA结构、接枝率进行了表征.同时对纳米载药体系DOX-CDots-FA体外药物释放行为、细胞毒性及细胞摄取成像进行了系统的研究.结果表明,DOX-CDots-FA具有良好的p H响应性.叶酸靶向基团能加速DOX-CDots-FA被He La(FR+)细胞摄取,并表现出更强的细胞毒性.同时细胞摄入成像实验表明,在叶酸靶向作用下,DOX-CDots-FA通过内吞作用进入He La细胞,随后阿霉素被释放出来并进入细胞核区域,抑制细胞的生长,从而实现靶向治疗,降低毒副作用. A one-step microwave method was successfully prepared with the surface of the amino group of carbon nano-dots CDots, and the target group by amidation folic acid grafted onto the carbon surface, successfully obtained the intermediate product CDots-FA. On this basis, Synthesis of four-arm hydrazide-based compounds 2 and doxorubicin (DOX) connection, to achieve the chemical bond of doxorubicin drug molecules on the surface of the carbon point, and finally obtain a multifunctional nano-drug delivery system DOX-CDots-FA. The properties of CDots were characterized by atomic force microscopy (AFM), high-resolution transmission electron microscopy (HR-TEM) and fluorescence spectroscopy. The structure of DOX-CDots-FA was grafted by gravimetry and UV- The drug release behavior, cytotoxicity and cell uptake imaging of drug-loaded DOX-CDots-FA in vitro were systematically studied.The results showed that DOX-CDots-FA had good p H response.Foliate Targeting groups can accelerate the uptake of DOX-CDots-FA by HeLa (FR +) cells and show more cytotoxicity.At the same time, the cytotoxicity of DOX-CDots-FA by DOX-CDots- Endocytosis into He La cells, Then doxorubicin is released and enter the nucleus, inhibit the growth of cells in order to achieve targeted therapy and reduce side effects.
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