文献：Efficient Delivery of an Antisense Oligodeoxyribonucleotide Formulated in Folate Receptor-targeted Liposomes

著者：SHIH-JIUAN CHIU, GUIDO MARCUCCI and ROBERT J. LEE论文地址：引言：Background: Folate receptors (FRs) are cellular surface markers for numerous solid tumors and myeloid leukemias. The aim of this study was to develop an antisense oligodeoxyribonucleotide (ODN) carrier targeting FR-overexpressing cancer cells using folate (FA) as the targeting moiety. G3139, a phosphorothioate antisense ODN against human bcl2 mRNA, was evaluated in this study. Materials and Methods: G3139-containing liposomes were prepared using an ethanol dilution method. For the targeted formulation, 0.5 mol% of folate-PEG-DSPE was incorporated as a targeting ligand into cationic liposomes composed of DC-Chol/egg PC/PEG-DSPE at 25:65:10 mol/mol. Particle size and surface charge were measured and cellular uptake was assessed by fluorescence microscopy and flow cytometry. The ODN-containing formulations were evaluated in FR+ KB cells for Bcl2 down-regulation measured by Western blot. The cytotoxicity of the formulations was determined by MTT assay. Results: The G3139-containing liposomes had an average diameter of 80-90 nm with high ODN entrapment efficiency (70-80%). Incorporation of the folate ligand did not significantly alter the particle size and entrapment efficiency. The formulation exhibited colloidal stability in a serum-containing environment. In uptake studies, the folate-targeted formulation showed ligand concentration-dependent uptake that was up to 6-fold more efficient than that of the non-targeted formulation (p<0.05). The uptake could be blocked by an excess amount of free folate, thus indicating an FR-dependent mechanism. Conclusion: FR-targeted G3139-containing liposomes showed promising transfection activity in KB cells. FR-targeted formulations were capable of specific targeting to FR-overexpressing cell lines and optimizing the amount of folate ligand in the liposomal formulation can result in more efficient antisense delivery.

本探索分析的意图是研发一些反义寡脱氧核糖核苷酸（ODN）媒介，以孕妇叶酸（FA）为靶向治疗药物那部分，靶向治疗药物过把你想表达出来FR的细胞膜。本探索分析评估报告格式了针对于人bcl2 mRNA的硫代反义寡核苷酸G3139。原料和最简单的方法：选用工业乙醇稀释液法制建设备含G3139的脂质体。来说靶向治疗疗法剂型，以25:65:10 mol/mol的的比例将0.5 mol%的DHA-PEG-DSPE充当靶向治疗疗法配体掺进由DC-Chol/egg PC/PEG-DSPE结构的阳阴离子脂质体中。自动测量颗粒直径和表明自由电荷，并进行荧光显微镜和流式神经元神经元术评价神经元摄取量。进行球营养物质印刷痕迹法在FR+KB神经元中评价含ODN的剂型的Bcl2再降现象。进行MTT法测试剂型的神经元毒素。后果：含G3139的脂质体评均长度为80-90nm，ODN包封率高（70-80%）。DHA配体的加入适量还没有有效影响比表面积和包封利用率。该药物制剂在含血清的坏境中表达出溶液不稳性。在摄入探究中，备孕叶酸片靶点疗法药品屏幕上显示出配体密度依靠性摄入，其效应比非靶点疗法药品超出6倍（p<0.05）。过多的徘徊备孕叶酸片可传导摄入，才能反映出FR依靠规则。答案：含FR靶点药物疗法G3139的脂质体在KB神经元中表明出优秀的转染活力性。FR靶点药物疗法药物制剂够特情人靶点药物疗法FR过呈现的神经元系，优化系统脂质体药物制剂中叶酸片配体的量应该导致更可行的反义递送。关联推介：Cy7-DSPECy7-PEG-DOPECy7-PEG-DPPEDSPE-PEG-Cy7DSPE-PEG-cRGDDPPE-PEG-cRGDDMPE-PEG-cRGDDOPE-PEG-cRGD

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