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Nature Nanotechnology:新型RNAi药物纳米载体

来源:科学时报 2009-08-26 09:50

研究人员在8月在线出版的《自然—纳米技术》期刊上报告,将一种新配方制成的磁性纳米颗粒用于输送核酸药物,可抑制小鼠肿瘤的生长。他们发现,与采用商业化的纳米颗粒药物运输器相比,用这种纳米颗粒输送癌症基因沉默因子RNA能更有效地抗击肿瘤。新发明有望提高针对各种癌症的基因药物发送系统的效率。

癌症基因治疗的成功取决于如何有效地将小型干扰RNA(siRNA)运送到导致疾病的特定基因,并将它们关闭。Yoshihisa Namiki和同事将携带最优化序列siRNA的磁性纳米颗粒注入小鼠的血管中,然后通过磁铁引导携带siRNA的纳米颗粒进入肿瘤,这种磁铁粘贴或是种植在肿瘤附近的皮肤下面。这种siRNA经专门设计,用于沉默肿瘤血管中特定基因的表达;经过8次最优化剂量的注射后,这种特定的siRNA会到达目的地,并阻断肿瘤血管的生长。

Namiki小组的工作显示,经过这种治疗,肿瘤的生长速度在无任何副免疫反应和副作用的情况下得到了抑制。进一步的研究还确认:这种基因沉默的原因在于RNA干涉。他们相信,这种新型磁性纳米颗粒比目前已有的磁性纳米颗粒有更好的抗肿瘤效果,并有望广泛应用于多种癌症基因治疗的基因发送系统中。(生物谷Bioon.com)

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Nature Nanotechnology 23 August 2009 | doi:10.1038/nnano.2009.202

A novel magnetic crystal–lipid nanostructure for magnetically guided in vivo gene delivery

Yoshihisa Namiki1, Tamami Namiki2, Hiroshi Yoshida3, Yukiko Ishii1,2, Akihito Tsubota1, Shigeo Koido4, Kouichi Nariai5, Makoto Mitsunaga4, Satoru Yanagisawa6, Hideyuki Kashiwagi6, Yasuo Mabashi1, Yoko Yumoto1, Sadayori Hoshina1, Kiyotaka Fujise1,4 & Norio Tada1,7

Abstract

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.

1 Institute of Clinical Medicine and Research, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba 277-8567, Japan
2 Department of Radiology, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba 277-8567, Japan
3 Department of Laboratory Medicine, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba 277-8567, Japan
4 Division of Gastroenterology and Hepatology, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba 277-8567, Japan
5 Laboratory Animal Facilities, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba 277-8567, Japan
6 Department of Surgery, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba 277-8567, Japan
7 Division of General Medicine, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba 277-8567, Japan

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