Non-cytotoxic polymer vesicles for rapid and efficient intracellular delivery
Non-cytotoxic polymer vesicles for rapid and efficient intracellular delivery
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DOI：
10.1039/b717431d
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发表时间：
2008-01-01
影响因子：
3.4
通讯作者：
Battaglia, Giuseppe
中科院分区：
文献类型：
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作者：
Lomas, Hannah;Massignani, Marzia;Battaglia, Giuseppe
我们最近已经通过使用pH敏感的聚（2-（甲基丙烯酰氧基）乙基磷酰胆碱）-共-聚（2-（二异丙基氨基）乙基甲基丙烯酸酯）（PMPC-PDPA）二嵌段共聚物，自组装形成囊泡，称为聚合物囊泡，在水溶液中实现了有效的胞质递送。特别值得注意的是，这些二嵌段共聚物在生理pH下形成稳定的聚合物囊泡，但在低于pH 6时迅速解离，得到分子溶解的共聚物链（单聚体）。这些PMPC-PDPA聚合物囊泡用于包封核酸以进行有效的细胞内递送。共聚焦激光扫描显微镜和荧光流式细胞术用于定量细胞摄取和研究这一过程的动力学。最后，我们研究了PMPC-PDPA聚合物囊泡如何影响原代人细胞（人真皮成纤维细胞（HDF））的活力，特别关注是否引发炎症反应。
We have recently achieved efficient cytosolic delivery by using pH-sensitive poly(2-(methacryloyloxy) ethylphosphorylcholine)-co-poly(2-( diisopropylamino)ethylmethacrylate) (PMPC-PDPA) diblock copolymers that self-assemble to form vesicles, known as polymersomes, in aqueous solution. It is particularly noteworthy that these diblock copolymers form stable polymersomes at physiological pH but rapidly dissociate below pH 6 to give molecularly-dissolved copolymer chains (unimers). These PMPC-PDPA polymersomes are used to encapsulate nucleic acids for efficient intracellular delivery. Confocal laser scanning microscopy and fluorescence flow cytometry are used to quantify cellular uptake and to study the kinetics of this process. Finally, we examine how PMPC-PDPA polymersomes affect the viability of primary human cells (human dermal fibroblasts (HDF)), paying particular regard to whether inflammatory responses are triggered.