A novel magnetic crystal-lipid nanostructure for magnetically guided in vivo gene delivery
A novel magnetic crystal-lipid nanostructure for magnetically guided in vivo gene delivery
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DOI：
10.1038/nnano.2009.202
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发表时间：
2009-09-01
影响因子：
38.3
通讯作者：
Tada, Norio
中科院分区：
文献类型：
--
作者：
Namiki, Yoshihisa;Namiki, Tamami;Tada, Norio
癌症基因治疗需要安全有效的基因递送系统。聚合物和脂质包覆的磁性纳米晶体已被用于递送沉默RNA，但合成这些磁性载体是困难的。在这里，我们展示了一种新的纳米颗粒制剂可以被磁性引导来传递和沉默小鼠细胞和肿瘤中的基因。该制剂称为LipoMag，由油酸包被的磁性脂质核和阳离子脂质壳组成。当与市售PolyMag制剂相比时，LipoMag在13种细胞系中的9种中显示出更有效的基因沉默，并且当全身施用给携带胃肿瘤的小鼠时具有更好的抗肿瘤作用。通过递送靶向肿瘤血管的表皮生长因子受体的沉默RNA的优化序列，实现了预期的治疗益处，没有明显的不良免疫反应或不良副作用。
Cancer gene therapy requires a safe and effective gene delivery system. Polymer- and lipid-coated magnetic nanocrystals have been used to deliver silencing RNA, but synthesizing these magnetic vectors is difficult. Here, we show that a new nanoparticle formulation can be magnetically guided to deliver and silence genes in cells and tumours in mice. This formulation, termed LipoMag, consists of an oleic acid-coated magnetic nanocrystal core and a cationic lipid shell. When compared with the commercially available PolyMag formulation, LipoMag displayed more efficient gene silencing in 9 of 13 cell lines, and better anti-tumour effects when systemically administered to mice bearing gastric tumours. By delivering an optimized sequence of a silencing RNA that targets the epidermal growth factor receptor of tumour vessels, the intended therapeutic benefit was achieved with no evident adverse immune reaction or untoward side effects.