Application of apolipoprotein E-modified liposomal nanoparticles as a carrier for delivering DNA and nucleic acid in the brain.
Application of apolipoprotein E-modified liposomal nanoparticles as a carrier for delivering DNA and nucleic acid in the brain.
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应用载脂蛋白E修饰的脂质体纳米颗粒作为大脑中递送DNA和核酸的载体。
DOI：
10.2147/ijn.s65402
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发表时间：
2014
影响因子：
8
通讯作者：
Harashima H
中科院分区：
文献类型：
--
作者：
Tamaru M;Akita H;Nakatani T;Kajimoto K;Sato Y;Hatakeyama H;Harashima H
迫切需要一种创新的给药技术来满足治疗各种脑部疾病的医疗需求。作为质粒DNA或核酸的基本载体，我们开发了一种含有质子电离氨基脂质（YSK-MEND）的脂质体纳米颗粒（多功能包膜型纳米器件[MEND]）。在这里，我们报道了载脂蛋白E （ApoE）修饰对YSK-MEND靶向脑细胞功能的影响。ApoE修饰可显著改善小鼠神经元源性细胞系（neuro2a和CAD）中包裹短干扰RNA或质粒DNA的YSK-MEND的细胞摄取和功能。与未经ApoE修饰的YSK-MEND相比，脑室内给药ApoE修饰的YSK-MEND （ApoE/YSK-MEND）包封质粒DNA也导致更高的转基因表达。此外，观察荧光标记的ApoE/YSK-MEND和来自质粒DNA的mCherry（荧光蛋白）的表达表明，这种载体可能有助于在神经干细胞和/或神经祖细胞中传递和赋予转基因表达。因此，该系统可能是治疗神经退行性疾病的有用工具。
An innovative drug delivery technology is urgently needed to satisfy unmet medical needs in treating various brain disorders. As a fundamental carrier for plasmid DNA or nucleic acids, we developed a liposomal nanoparticle (multifunctional envelope-type nano device [MEND]) containing a proton-ionizable amino lipid (YSK-MEND). Here we report on the impact of apolipoprotein E (ApoE) modification on the function of YSK-MEND in terms of targeting brain cells. The cellular uptake and function of YSK-MEND encapsulating short interference RNA or plasmid DNA were significantly improved as a result of ApoE modification in mouse neuron-derived cell lines (Neuro-2a and CAD). Intracerebroventricular administration of ApoE-modified YSK-MEND (ApoE/YSK-MEND) encapsulating plasmid DNA also resulted in higher transgene expression in comparison with YSK-MEND that was not modified with ApoE. Moreover, observation of fluorescence-labeled ApoE/YSK-MEND and expression of mCherry (fluorescence protein) derived from plasmid DNA indicated that this carrier might be useful for delivering and conferring transgene expression in neural stem cells and/or neural progenitor cells. Thus, this system may be a useful tool for the treatment of neurodegenerative disease.