核酸适配体修饰聚酰胺-胺负载5-氟尿嘧啶纳米给药体系的制备表征及体外抗肝癌作用

目的研究核酸适配体(ZY1)修饰聚酰胺-胺(PAMAM)负载5-氟尿嘧啶-1-基乙酸(FUA)纳米给药体系(ZY1-PAMAM-FUA)的制备表征及其体外抗肝癌作用。方法将FUA、聚乙二醇(PEG)与PAMAM通过酰胺反应键合,然后将ZY1通过静电吸附与PEG-PAMAM-FUA缀合得到ZY1-PAMAM-FUA纳米给药体系。核磁共振氢谱仪(¹H-NMR)和傅里叶红外光谱仪(FT-IR)鉴定ZY1-PAMAM-FUA的化学结构,动态光散射技术(DLS)表征其粒径分布以及稳定性,紫外分光光度法检测其载药量和体外释药性能,流式细胞仪和荧光显微镜考察SMMC-7221肝癌细胞对Cy5标记的纳米给药体系的摄取能力；MTT法检测纳米给药体系对SMCC-7721肝癌细胞增殖活性的影响。结果ZY1-PAMAM-FUA粒径分布均匀,粒径为102.3 nm,其载药量为8.70%±0.43%,并具有良好的缓释性能。与PAMAM-FUA比较,ZY1-PAMAM-FUA可以更高效地靶向SMCC-7721细胞。ZY1-PAMAM-FUA具有良好的生物相容性且对SMCC-7721细胞具有良好的抗细胞增殖作用。结论ZY1-PAMAM-FUA制备方法简单稳定,具有良好的生物相容性,可以高效地将药物靶向SMCC-7721细胞发挥抗肝癌细胞增殖的作用。

Fabrication and characterization of aptamer modified polyamide-amine loaded 5-fluorouracil drug delivery system for hepatocellular carcinoma therapy in vitro

To study fabrication and characterization of the aptamer(ZY1) modified polyamide-amine (PAMAM) loaded 5-fluorouracil-1-glycolic acid (FUA) drug elivery system (ZY1-PAMAM-FUA) for hepatocellular carcinoma therapy in vitro. MethodsFUA, PEG and PAMAM are bonded through amide reaction, and then ZY1 is conjugated with PEG-PAMAM-FUA through electrostatic adsorption to obtain ZY1-PAMAM-FUA drug delivery system. The structure of ZY1-PAMAM-FUA was identified by nuclear magnetic resonance spectrometer (¹H-NMR) and fourier infrared spectrometer (FT-IR). The particle size distribution and the stability of ZY1-PAMAM-FUA were characterized by dynamic light scattering (DLS). The drug loading and cumulation drug release in vitro were detected by ultraviolet spectrophotometry (UV). The cellular uptake ability of Cy5-labeled ZY1-PAMAM-FUA drug delivery system on SMMC-7221 cells were investigated by Flow cytometry and Fluorescence microscope. The effect of ZY1-PAMAM-FUA drug delivery system on the proliferation of SMCC-7721 cells was detected by MTT. ResultsZY1-PAMAM-FUA drug delivery system has uniform particle size distribution and good sustained release performance with particle size of 102.3 nm and drug loading of 8.70%±0.43%. Compared with PAMAM-FUA, ZY1-PAMAM-FUA can target SMCC-7721 cells more efficiently. ZY1-PAMAM-FUA has splendid biocompatibility and excellent anti-proliferation effect on SMCC-7721 cells.ConclusionsThe preparation method of ZY1-PAMAM-FUA is simple, and the ZY1-PAMAM-FUA drug delivery system has splendid stability and biocompatibility. It can effectively deliver drugs to SMCC-7721 cells to inhibit the proliferation of hepatocellular carcinoma cells.