Lipid-coated nano-calcium-phosphate (LNCP) for gene delivery.

Lipid-coated nano-calcium-phosphate (LNCP) for gene delivery.
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DOI:
10.1016/j.ijpharm.2010.03.012
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发表时间:
2010-06-15
影响因子:
5.8
通讯作者:
Lee, Robert J.
Lee, Robert J.
中科院分区:
医学2区
文献类型:
--
作者:
Zhou, Chenguang;Yu, Bo;Yang, Xiaojuan;Huo, Tianyao;Lee, L. James;Barth, Rolf F.;Lee, Robert J.

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虽然磷酸钙已被用于递送质粒 DNA (pDNA) 数十年,但相对于其他非病毒方法(例如脂质体和聚合物),该方法的典型特点是转染效率低且不可重复。在此,我们报道了一种包含脂质包被的纳米磷酸钙(LNCP)的新型基因转移载体,该载体可提供一致有效且令人满意的 pDNA 递送。它基于包含磷酸钙核和阳离子脂质壳的核-壳纳米颗粒。与过去使用的溶液沉淀方法相比,该方法在阳离子脂质体内产生胶体稳定的磷酸钙纳米颗粒。我们的结果表明,即使在储存 21 天后,LNCP 的粒径和粒径分布几乎保持不变。原子力显微镜测量表明,LNCP 的刚性比普通阳离子脂质体高 5 倍。 LNCP 转染的 pDNA 比裸露 pDNA 多 24 倍,比标准磷酸钙沉淀制剂多 10 倍,表明 LNCP 可能具有作为基因治疗的新型转染剂的潜力。
While calcium-phosphate has been used to deliver plasmid DNA (pDNA) for decades, the method is typically characterized by low and irreproducible transfection efficiency relative to the other non-viral approaches, such as liposomes and polymers. Here we report a novel gene transfer vector comprising lipid-coated nano-calcium-phosphate (LNCP) that provides consistently efficient and satisfactory pDNA delivery. It is based on core-shell nanoparticles comprising a calcium-phosphate core and a cationic lipid shell. This method, in contrast to the solution precipitation methods used in the past, yields colloidally stable calcium-phosphate nanoparticles inside the cationic liposomes. Our results indicate that the particle size and the size distribution of the LNCP remain virtually unchanged even after 21 days of storage. Atomic force microscopy measurements reveal that the LNCP have a 5-fold higher rigidity than common cationic liposomes. The LNCP transfected pDNA 24 times greater than the naked pDNA and 10-fold greater relative to the standard calcium-phosphate precipitation preparations, suggesting that the LNCP may have potential as a novel transfection agent for gene therapy.
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