siRNA Delivery into Tumor Cells by Cationic Cholesterol Derivative-Based Nanoparticles and Liposomes
siRNA Delivery into Tumor Cells by Cationic Cholesterol Derivative-Based Nanoparticles and Liposomes
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DOI：
10.1248/bpb.b14-00526
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发表时间：
2015-01-01
影响因子：
2
通讯作者：
Yonemochi, Etsuo
中科院分区：
文献类型：
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作者：
Hattori, Yoshiyuki;Hara, Eriko;Yonemochi, Etsuo
以前，我们报道了由二胺型胆固醇-3-甲酰胺（OH-Chol，N-（2-（2-羟乙基氨基）乙基）胆固醇-3-甲酰胺）和吐温80组成的阳离子纳米颗粒（NP）可以将高转染效率的小干扰RNA（siRNA）递送到肿瘤细胞中。本研究合成了新型二胺型阳离子胆甾醇氨基甲酸酯（OH-C-Chol，胆固醇（2-（2-羟乙基）氨基）乙基）氨基甲酸酯）和三胺型氨基甲酸酯（OH-NC-Chol，胆固醇基（2-（（2-（2-羟乙基）氨基）乙基）氨基）乙基）氨基甲酸酯），以及制备的由OH-C-Chol或OH-NC-Chol与吐温80组成的阳离子纳米颗粒（分别为NP-C和NP-NC），以及由OH-C-Chol或OH-NC-Chol与1，2-二油酰基-sn-甘油基-3-磷酸乙醇胺（DOPE）组成的阳离子脂质体（分别为LP-C和LP-NC），用于评价它们作为siRNA递送载体的可能用途。在人乳腺肿瘤MCF-7细胞中，LP-C和LP-NC/siRNA复合物（脂质复合物）分别比NP-C和NP-NC/siRNA复合物（纳米复合物）表现出更大的基因沉默效应，尽管NP-C纳米复合物显示出与细胞的高度相关性。特别是，LP-NC lipoplex可以诱导强烈的基因抑制，即使在5 nm siRNA的浓度。因此，由OH-NC-Chol和DOPE组成的阳离子脂质体可能具有作为siRNA转染肿瘤细胞的基因载体的潜力。
Previously, we reported that cationic nanoparticles (NP) composed of diamine-type cholesteryl-3-carboxamide (OH-Chol, N-(2-(2-hydroxyethylamino)ethyl)cholesteryl-3-carboxamide) and Tween 80 could deliver small interfering RNA (siRNA) with high transfection efficiency into tumor cells. In this study, we synthesized new diamine-type cationic cholesteryl carbamate (OH-C-Chol, cholesteryl (2-(2-hydroxyethyl)amino)ethyl)carbamate) and triamine-type carbamate (OH-NC-Chol, cholesteryl (2-((2-(2-hydroxyethyl)amino)ethyl)amino)ethyl)carbamate), and prepared cationic nanoparticles composed of OH-C-Chol or OH-NC-Chol with Tween 80 (NP-C and NP-NC, respectively), as well as cationic liposomes composed of OH-C-Chol or OH-NC-Chol with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) (LP-C and LP-NC, respectively) for evaluation of their possible use as siRNA delivery vectors. LP-C and LP-NC/siRNA complexes (lipoplexes) exhibited larger gene silencing effects than NP-C and NP-NC/siRNA complexes (nanoplexes), respectively, in human breast tumor MCF-7 cells, although the NP-C nanoplex showed high association with the cells. In particular, LP-NC lipoplex could induce strong gene suppression, even at a concentration of 5 nm siRNA. From these results, cationic liposomes composed of OH-NC-Chol and DOPE may have potential as gene vectors for siRNA transfection to tumor cells.