This paper deals with a concept to improve the loading capability of cationic nanohydrogel particles with siRNA. For this purpose, a new tetrafunctional crosslinker is synthesized via a peptide coupling approach using lysine and spermine derivatives. Applying this four‐arm crosslinker to the particle synthesis makes it possible to perform the crosslinking with an excess or a deficit of the crosslinker. This allows for varying numbers of cationic groups per cationic core and its crosslinking density while the stability of the carrier system remains. The obtained cationic nanohydrogel particles are narrowly distributed in size as determined by dynamic light scattering measurements. Zeta potential measurements confirm the cationic nature of these carriers (ζ > +30 mV) and the ability to form complex anionic siRNA (agarose gel electrophoresis). As a result, it becomes possible to increase the siRNA loading by a factor of four by varying the composition of the crosslinked core. Such an increased siRNA loading should lead to an improved therapeutic gene knockdown effect.

中文翻译：

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改变交联密度，提高阳离子纳米水凝胶颗粒的SiRNA负载

本文提出了一种利用siRNA改善阳离子纳米水凝胶颗粒的负载能力的概念。为此，使用赖氨酸和精胺衍生物通过肽偶联方法合成了新的四官能交联剂。将这种四臂交联剂应用于颗粒合成可以在交联剂过量或不足的情况下进行交联。这使得每个阳离子核的阳离子基团数目及其交联密度可以变化，同时保持载体体系的稳定性。如通过动态光散射测量所确定的，所获得的阳离子纳米水凝胶颗粒的尺寸狭窄地分布。Zeta电势测量证实了这些载体的阳离子性质（ζ> +30 mV）和形成复杂阴离子siRNA的能力（琼脂糖凝胶电泳）。结果，通过改变交联核心的组成，有可能将siRNA负载增加四倍。如此增加的siRNA载量应导致改善的治疗基因敲低效应。