Safe and effective delivery of small interfering RNA with polymer- and liposomes-based complexes.
Safe and effective delivery of small interfering RNA with polymer- and liposomes-based complexes.
复制标题
DOI：
10.1248/bpb.b13-00054
复制
发表时间：
2013-06
影响因子：
2
通讯作者：
Yukinobu Kodama;Satoe Harauchi;Saki Kawanabe;N. Ichikawa;Hiroo Nakagawa;Takahiro Muro;N. Higuchi;Tadahiro Nakamura;T. Kitahara;H. Sasaki
中科院分区：
文献类型：
--
作者：
Yukinobu Kodama;Satoe Harauchi;Saki Kawanabe;N. Ichikawa;Hiroo Nakagawa;Takahiro Muro;N. Higuchi;Tadahiro Nakamura;T. Kitahara;H. Sasaki
我们开发了基于聚合物和脂质体的二元和三元复合物，用于安全有效地递送小干扰 RNA (siRNA)。抗荧光素酶siRNA被用作核酸医学的模型。 siRNA的二元复合物是用阳离子聚合物和阳离子脂质体制备的，例如聚乙烯亚胺(PEI)、聚酰胺胺(PAMAM)树枝状聚合物、聚-L-精氨酸(PLA)、三甲基[2,3-(二油氧基)-丙基]氯化铵(DOTMA)和胆固醇 3β-N-(二甲基氨基乙基)氨基甲酸酯盐酸盐(DC-Chol)。三元复合物是通过在二元复合物中添加γ-聚谷氨酸（γ-PGA）构建的。复合物的粒径约为54-153 nm。尽管在三元络合物中观察到阴离子表面电荷，但二元络合物显示出阳离子表面电荷。基于聚合物的复合物在定期表达荧光素酶的小鼠结肠癌细胞系（Colon26/Luc细胞）中没有表现出沉默作用。基于脂质体的二元复合物以及γ-PGA包覆的三元复合物表现出显着的沉默效果。尽管γ-PGA包被的三元复合物没有表现出显着的细胞毒性，但二元复合物表现出显着的细胞毒性。 γ-PGA 包被的三元复合物直接注射到带有 Colon26/Luc 细胞的小鼠肿瘤中后，抑制了肿瘤中的荧光素酶活性。因此，我们新发现了安全有效的siRNA三元复合物供临床使用。
We developed binary and ternary complexes based on polymers and liposomes for safe and effective delivery of small interfering RNA (siRNA). Anti-luciferase siRNA was used as a model of nucleic acid medicine. The binary complexes of siRNA were prepared with cationic polymers and cationic liposomes such as polyethylenimine (PEI), polyamidoamine (PAMAM) dendrimer, poly-L-arginine (PLA), trimethyl[2,3-(dioleoxy)-propyl]ammonium chloride (DOTMA), and cholesteryl 3β-N-(dimetylaminnoethyl)carbamate hydrochloride (DC-Chol). The ternary complexes were constructed by the addition of γ-polyglutamic acid (γ-PGA) to the binary complexes. The complexes were approximately 54-153 nm in particle size. The binary complexes showed a cationic surface charge although an anionic surface charge was observed in the ternary complexes. The polymer-based complexes did not show a silencing effect in the mouse colon carcinoma cell line expressing luciferase regularly (Colon26/Luc cells). The binary complexes based on liposomes and their ternary complexes coated by γ-PGA showed a significant silencing effect. The binary complexes showed significant cytotoxicity although the ternary complexes coated by γ-PGA did not show significant cytotoxicity. The ternary complexes coated by γ-PGA suppressed luciferase activity in the tumor after their direct injection into the tumors of mice bearing Colon26/Luc cells. Thus, we have newly identified safe and efficient ternary complexes of siRNA for clinical use.