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 ∼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 °C (>lower 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.

中文翻译：

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将可热切换疏水域安装到Unimer聚离子复合物中，以增强siRNA的细胞摄取。

尺寸为10-20 nm的小型siRNA纳米载体具有较高的组织渗透性，但它们却面临着细胞表面吸附效率低下的挑战，从而导致细胞对siRNA的吸收较差。为了解决这一难题，本研究旨在控制大小约为10 nm的小siRNA纳米载体单聚体聚离子复合物（uPIC）的疏水性。uPIC由siRNA和智能三嵌段共聚物（包括亲水性聚（2-乙基-2-恶唑啉）（PEtOx），可热转换的聚（2-n-丙基-2-恶唑啉）（PnPrOx））之间的一对构成。和阳离子聚（1-赖氨酸）（PLL）。PnPrOx片段在37°C（>较低的临界溶液温度）下脱水以增强uPIC的疏水性。