Installation of a Thermoswitchable Hydrophobic Domain into a Unimer Polyion Complex for Enhanced Cellular Uptake of siRNA
Installation of a Thermoswitchable Hydrophobic Domain into a Unimer Polyion Complex for Enhanced Cellular Uptake of siRNA
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DOI：
10.1021/acs.bioconjchem.0c00238
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发表时间：
2020-05-01
影响因子：
4.7
通讯作者：
Miyata, Kanjiro
中科院分区：
文献类型：
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作者：
Kim, Beob Soo;Osawa, Shigehito;Miyata, Kanjiro
Whereas small siRNA nanocarriers with a size of 10-20 nm exert high tissue-permeability, they encounter the challenge of inefficient adsorption on the cell surface, resulting in poor cellular uptake of siRNA. To solve this dilemma, this study aims to control the hydrophobicity of a small siRNA nanocarrier, unimer polyion complex (uPIC), with a size of similar to 10 nm. The uPICs are fabricated to consist of a single pair between siRNA and a smart triblock copolymer comprising hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx), thermoswitchable poly(2-n-propyl-2-oxazoline) (PnPrOx), and cationic poly(L-lysine) (PLL). The PnPrOx segment is dehydrated at 37 degrees C (>Iower critical solution temperature) to enhance the hydrophobicity of uPICs. The uPICs with a hydrophobic domain facilitates cellular uptake of the siRNA payload through stronger binding to the cell surface, compared with control uPICs without a PnPrOx segment, leading to a significantly enhanced gene silencing effect in cultured cancer cells.
