Herein we report the 2-nitrobenzenesulfonamide group as a new chemical linker that responds to the difference in redox potential across the cellular membrane, toward the construction of siRNA-polymer conjugates. PEG-conjugated to siRNA via the 2-nitrobenzenesulfonamide group (PEG-sul-siRNA) exhibited highly selective siRNA release under intracellular conditions due to the exclusive presence of the GSH/GST combination in the cell. In addition, siRNA release from PEG-sul-siRNA under extracellular reductive conditions was dramatically suppressed relative to PEG-siRNA conjugates containing a conventional redox-sensitive disulfide linkage (PEG-disulfide-siRNA), indicating the enhanced extracellular stability of the 2-nitrobenzenesulfonamide group. The enhanced gene-silencing effect of PEG-sul-siRNA for cultured cells relative to PEG-siRNA, containing a non-cleavable carboxylic amide linkage (PEG-car-siRNA), confirmed the intracellular release of siRNA via the PEG-sul-siRNA system. These results suggest that the 2-nitrobenzenesulfonamide group could be a suitable chemical linker alternative to the conventional disulfide group.

中文翻译：

---

2-硝基苯磺酰胺基团用作在siRNA偶联的聚合物系统中增强的细胞外稳定性和胞质裂解的化学接头。

在本文中，我们报告了2-硝基苯磺酰胺基团作为一种新的化学接头，可响应跨细胞膜的氧化还原电位差异，从而构建siRNA-聚合物共轭物。通过2-硝基苯磺酰胺基团（PEG-sul-siRNA）与siRNA偶联的PEG在细胞内条件下表现出高度选择性的siRNA释放，这是由于细胞中仅存在GSH / GST组合。此外，相对于含有常规氧化还原敏感的二硫键（PEG-disulfide-siRNA）的PEG-siRNA共轭物，在胞外还原条件下从PEG-sul-siRNA释放的siRNA被显着抑制，表明2-硝基苯磺酰胺的胞外稳定性增强。团体。相对于PEG-siRNA，PEG-sul-siRNA对培养细胞的基因沉默作用增强，含有不可裂解的羧酰胺键（PEG-car-siRNA）的蛋白通过PEG-sul-siRNA系统证实了siRNA在细胞内的释放。这些结果表明2-硝基苯磺酰胺基团可能是常规二硫键基团的合适化学连接基。