Effect of Polymer Phase Transition Behavior on Temperature-Responsive Polymer-Modified Liposomes for siRNA Transfection
Effect of Polymer Phase Transition Behavior on Temperature-Responsive Polymer-Modified Liposomes for siRNA Transfection
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DOI：
10.3390/ijms20020430
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发表时间：
2019-01-02
影响因子：
5.6
通讯作者：
Kanazawa, Hideko
中科院分区：
文献类型：
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作者：
Nagase, Kenichi;Hasegawa, Momoko;Kanazawa, Hideko
小干扰rna （sirna）因其基因沉默特性而备受关注，可用于治疗顽固性疾病。本研究用不同的聚合物修饰脂质体-聚（n -异丙基丙烯酰胺-co- n， n -二甲氨基丙烯酰胺）（P(NIPAAm-co-DMAPAAm)）和聚（n -异丙基丙烯酰胺-co- n， n -二甲丙烯酰胺）P(NIPAAm-co-DMAAm)，制备了两种温度响应型脂质体siRNA载体。P（NIPAAm-co-DMAPAAm）的相变较P（NIPAAm-co-DMAAm）明显，这是由于共单体含量较低所致。所制备的脂质体的温度依赖性固定水层厚度（FALT）表明，用P（NIPAAm-co-DMAPAAm）修饰脂质体，在37℃~ 42℃之间，固定单层水层厚度发生了显著变化；而P（NIPAAm-co-DMAAm）修饰导致fart在更宽的温度范围内发生变化。温度响应性脂质体在42℃时表现出细胞摄取，但在37℃时不被细胞摄取。这可能是因为脂质体表面的热响应性亲水/疏水变化诱导了温度响应性细胞摄取。此外，siRNA转染细胞以防止荧光素酶和血管内皮生长因子（VEGF）的表达可通过外部温度变化来调节。与P（NIPAAm-co-DMAAm）修饰的类似物相比，P（NIPAAm-co-DMAAm）修饰的脂质体尤其表现出有效的siRNA转染特性和低细胞毒性。这些结果表明，制备的温度响应脂质体可以作为siRNA的有效载体，其转染特性可以通过温度调节。
Small interfering RNAs (siRNAs) have been attracting significant attention owing to their gene silencing properties, which can be utilized to treat intractable diseases. In this study, two temperature-responsive liposomal siRNA carriers were prepared by modifying liposomes with different polymers-poly(N-isopropylacrylamide-co-N,N-dimethylaminopropyl acrylamide) (P(NIPAAm-co-DMAPAAm)) and poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) P(NIPAAm-co-DMAAm). The phase transition of P(NIPAAm-co-DMAPAAm) was sharper than that of P(NIPAAm-co-DMAAm), which is attributed to the lower co-monomer content. The temperature dependent fixed aqueous layer thickness (FALT) of the prepared liposomes indicated that modifying liposomes with P(NIPAAm-co-DMAPAAm) led to a significant change in the thickness of the fixed aqueous monolayer between 37 degrees C and 42 degrees C; while P(NIPAAm-co-DMAAm) modification led to FALT changes over a broader temperature range. The temperature-responsive liposomes exhibited cellular uptake at 42 degrees C, but were not taken up by cells at 37 degrees C. This is likely because the thermoresponsive hydrophilic/hydrophobic changes at the liposome surface induced temperature-responsive cellular uptake. Additionally, siRNA transfection of cells for the prevention of luciferase and vascular endothelial growth factor (VEGF) expression was modulated by external temperature changes. P(NIPAAm-co-DMAPAAm) modified liposomes in particular exhibited effective siRNA transfection properties with low cytotoxicity compared with P(NIPAAm-co-DMAAm) modified analogues. These results indicated that the prepared temperature-responsive liposomes could be used as effective siRNA carriers whose transfection properties can be modulated by temperature.