多功能MRI可视化纳米基因载体的研究

兰州大学机构库 >生命科学学院

	多功能MRI可视化纳米基因载体的研究
Alternative Title	Multifunctional Nanoparticles as MRI Visible Transfection Agents
	万倩
Thesis Advisor	刘恒 ; 邱本胜
	2015-05-30
Degree Grantor	兰州大学
Place of Conferral	兰州
Degree Name	硕士
Keyword	纳米材料自组装分子影像基因治疗
Abstract	基因治疗已经被广泛的用于治疗一些包括癌症在内的人类疾病，其临床治疗成功的关键因素取决于具有安全且有效的基因传递载体系统。与病毒载体相比，非病毒载体具有使用安全、易于大规模生产、特异性化学修饰以及无免疫反应等优势。目前，高分子量聚乙烯亚胺（PEI）是最有效的非病毒载体之一，如PEI25K，但是由于高分子量PEI的在体内高的毒性作用，其临床应用受到限制。阻碍治疗发展的另一个重要障碍是无法通过非侵入手段获得体内基因载体准确的生物学分布和功能信息。本研究通过使用硬脂酸修饰低分子量的聚乙烯亚胺（PEI600）包裹四氧化三铁纳米颗粒形成纳米治疗体系，即Stearic-LWPEI-SPIO纳米复合物。然后运用此纳米复合物运载具有高转染效率和长表达时间的微环质粒DNA作为一个新的肿瘤基因治疗系统。研究发现Stearic-LWPEI-SPIO纳米复合物在体外人乳腺癌细胞（MCF-7 cells）转染试验中具有较低的毒性和较高的转染效率。凝胶电泳实验，动态光散射实验（DLS）以及磁共振成像实验也均证明了Stearic-LWPEI-SPIO纳米复合物在维持其纳米级粒度分布和良好的磁共振成像效果下，同时仍具有稳定的DNA结合、保护和传递能力。综上，我们认为合成的新型StearicPEI-SP-LWIO纳米复合物具有一定的应用于临床基因治疗的潜力。
Other Abstract	Gene therapy has become an important strategy for treating various of human diseases, for example, cancer. The clinical success of gene therapy intimately relies on the development of safe and efficient gene delivery systems. Compared with viral vectors, non-viral vectors are safe, simple to prepare and modify, and have larger gene encapsulation capability. Polyethylenimine (PEI) is one of the most efficient non-viral vectors. However, PEI is still limited as a gene carrier in clinical treatment, because of its high cytotoxicity in vivo. And, another important obstacle for treatment development is the inability to acquire the bioinformation about biodistribution and biofunction of the gene vectors in vivo non-invasively. In this study, we used stearic acid modified low molecular weight polyethylenimine (PEI600) to encapsulate SPIO nanocrystals to form nanoscopic therapeutic systems, Stearic-LWPEI-SPIO. Now Minicircle plasmid DNA is a powerful candidate for improving gene expression and prolonging the lifespan of gene expression. So The Stearic-LWPEI-SPIO systems combined with minicircle DNA. We found here that Stearic-LWPEI-SPIO nanocomposite nontoxic and highly potent in vitro gene transfection in MCF-7 cells. Via gel electrophoresis measurements, cell toxicity studies, dynamic light scattering measurements (DLS) and magnetic resonance imaging (MRI), the results show that Stearic-LWPEI-SPIO nanocomposites could stably bind, protect and deliver mcDNA for gene transfection, while maintaining good magnetic properties and biocompatibility. In conclusion, this new Stearic-LWPEI-SPIO nanocomposite may provide opportunities in gene therapy.
URL	查看原文
Language	中文
Document Type	学位论文
Identifier	https://ir.lzu.edu.cn/handle/262010/221520
Collection	生命科学学院
Recommended Citation GB/T 7714	万倩. 多功能MRI可视化纳米基因载体的研究[D]. 兰州. 兰州大学,2015.

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