Efficient cytoplasmic protein delivery by means of a multifunctional envelope-type nano device
Efficient cytoplasmic protein delivery by means of a multifunctional envelope-type nano device
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DOI：
10.1248/bpb.30.758
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发表时间：
2007-04-01
影响因子：
2
通讯作者：
Harashima, Hdeyoshi
中科院分区：
文献类型：
--
作者：
Suzuki, Ryosuke;Yamada, Yuma;Harashima, Hdeyoshi
蛋白质疗法的潜力，例如使用抗体和疫苗，现在已经被广泛接受。然而，如果没有合适的递送系统将蛋白质输送到靶部位，就很难提高蛋白质治疗的效率。在这里，我们描述了蛋白质递送系统的发展，它能够进行细胞质递送以及有效的包装。多功能包膜型纳米器件(MEND)最初是为输送质粒DNA和寡核苷酸等核酸而开发的，也可以应用于蛋白质输送。在本研究中，绿色荧光蛋白(GFP)是一种模型蛋白，它与硬脂酰八精氨酸(硬脂酰R8)缩合形成纳米颗粒，然后将其包裹在脂膜上，从而允许R8被引入以有效地摄取和控制细胞内的运输。Mend的包装效率明显高于传统脂质体，因为GFP可以以凝聚的形式被包裹。根据激光共聚焦扫描显微镜，补丁被有效地内化，并从酸性隔室逃逸，从而有效地将GFP释放到胞浆中。这些结果表明，MEND可以作为一种有用的蛋白质治疗的细胞质递送系统。
The potential for protein therapy, such as the use of antibodies, and vaccines is now well accepted. However, it is difficult to enhance efficiency in protein therapy without a suitable delivery system for delivering proteins to target sites. Here we describe the development of protein delivery system, which is capable of cytoplasmic delivery as well as efficient packaging. The multifunctional envelope-type nano device (MEND), which was originally developed for the delivery of nucleic acids such as plasmid DNA and oligodeoxynucleotides, can also be applied to protein delivery. In this study, the green fluorescent protein (GFP), a model protein, was condensed with stearyl octaarginine (stearyl R8) to form a nano particle, which was then coated with a lipid membrane, thus permitting R8 to be introduced for efficient cellular uptake and controlled intracellular trafficking. The packaging efficiency of the MEND was significantly higher than that of conventional liposomes, because the GFP can be encapsulated a condensed form. According to confocal laser scanning microscopy, the MEND is internalized efficiently and escapes from the acidic compartment to efficiently release GFP into the cytosol. These results indicate that the MEND can serve as a useful cytoplasmic delivery system for protein therapy.