Development of a successive targeting liposome with multi-ligand for efficient targeting gene delivery.
Development of a successive targeting liposome with multi-ligand for efficient targeting gene delivery.
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DOI：
10.1002/jgm.1569
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发表时间：
2011-05
影响因子：
3.5
通讯作者：
Jin, Yi
中科院分区：
文献类型：
--
作者：
Ma, Kun;Shen, Haijun;Shen, Song;Xie, Men;Mao, Chuanbin;Qiu, Liyan;Jin, Yi
一个成功的基因传递系统需要突破几个障碍，以允许有效的转基因表达。在本研究中，通过将各种靶向基团整合到纳米颗粒中来构建连续靶向脂质体（STL）以解决这个问题。通过两步反应合成了具有核靶向作用的聚乙烯亚胺（PEI）1800-曲安奈德（TA）。将乳糖酸与胆固醇连接，得到具有肝细胞靶向性的[（2-乳酰氨基）乙氨基]甲酸胆固醇酯（CHEDLA）。用PEI 1800-TA和CHEDLA对脂质体进行修饰，制备了连续靶向脂质体（STL）。并对其理化性质和转染效率进行了体内外研究。STL的直径约为100 nm，电位为20 mV。共聚焦显微镜观察和电位分析证实PEI 1800-TA修饰了STL的脂双层。STL的细胞毒性显著低于PEI 1800-TA和PEI 25 K。10%CHEDLA STL对HepG 2细胞的转染效率高于后两者。其转染效率大大降低与过量的游离半乳糖，表明STL是通过半乳糖受体介导的内吞吸收。小鼠体内实验表明，10%CHEDLA STL在肝脏中的转基因表达效果优于其他载体。多配体的STL能够克服靶向细胞核和特定细胞的各种障碍，并呈现出独特的转基因表达。因此，它作为一种非病毒载体在基因治疗中具有很大的潜力。
A successful gene delivery system needs to breakthrough several barriers to allow efficient transgenic expression. In the present study, successive targeting liposomes (STL) were constructed by integrating various targeting groups into a nanoparticle to address this issue. Polyethylenimine (PEI) 1800-triamcinolone acetonide (TA) with nuclear targeting capability was synthesized by a two-step reaction. Lactobionic acid was connected with cholesterol to obtain a compound of [(2-lactoylamido) ethylamino]formic acid cholesterol ester (CHEDLA) with hepatocyte-targeting capability. The liposome was modified with PEI 1800-TA and CHEDLA to prepare successive targeting liposome (STL). Its physicochemical properties and transfection efficiency were investigated both in vitro and in vivo. The diameter of STL was approximately 100 nm with 20 mV of potential. The confocal microscopy observation and potential assay verified that lipid bilayer of STL was decorated with PEI 1800-TA. Cytotoxicity of STL was significantly lower than that of PEI 1800-TA and PEI 25K. The transfection efficiency of 10% CHEDLA STL in HepG2 cells was the higher than of the latter two with serum. Its transfection efficiency was greatly reduced with excessive free galactose, indicating that STL was absorbed via galactose receptor-mediated endocytosis. The in vivo study in mice showed that 10% CHEDLA STL had better transgenic expression in liver than the other carriers. STL with multi-ligand was able to overcome the various barriers to target nucleus and special cells and present distinctive transgenic expression. Therefore, it has a great potential for gene therapy as a nonviral carrier.
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影响因子：
14
作者：
Akita, Hidetaka;Kudo, Asako;Harashima, Hideyoshi
通讯作者：
Harashima, Hideyoshi
影响因子：
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作者：
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作者：
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通讯作者：
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作者：
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通讯作者：
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