分支型聚乙烯亚胺（bPEI）经常用于RNA干扰（RNAi）实验中作为阳离子聚合物，用于传递小干扰RNA（siRNA），因其能够形成稳定的聚合物，促进siRNA的摄取。然而，bPEI在基因传递中的应用受到其细胞毒性和目标特异性的限制。本文中，bPEI被d-果糖修饰以提高生物相容性，并通过过表达GLUT5转运蛋白来靶向乳腺癌细胞。通过三步从商业可获得的保护果糖衍生物和bPEI开始，合成并通过NMR光谱、凝胶渗透色谱和元素分析进行表征具有不同分子量、取代程度和连接位置（C1和C3）的若干聚合物。体外生物学筛选显示，果糖修饰后的10 kDa bPEI具有显著降低的细胞毒性，siRNA聚合物的特异性摄取，以及与非癌细胞（HEK-293T）相比，在三阴性乳腺癌细胞（MDA-MB-231）中靶向的GFP沉默。本文受版权保护。版权所有。

Branched poly(ethylene imine) (bPEI) is frequently used in RNA interference (RNAi) experiments as a cationic polymer for the delivery of small interfering RNA (siRNA) because of its ability to form stable polyplexes that facilitate siRNA uptake. However, the use of bPEI in gene delivery is limited by its cytotoxicity and a need for target specificity. In this work, bPEI is modified with d-fructose to improve biocompatibility and target breast cancer cells through the overexpressed GLUT5 transporter. Fructose-substituted bPEI (Fru-bPEI) is accessible in three steps starting from commercially available protected fructopyranosides and bPEI. Several polymers with varying molecular weight, degree of substitution, and linker positions on d-fructose (C1 and C3) are synthesized and characterized with NMR spectroscopy, size exclusion chromatography, and elemental analysis. In vitro biological screenings show significantly reduced cytotoxicity of 10 kDa bPEI after fructose functionalization, specific uptake of siRNA polyplexes, and targeted GFP knockdown in triple-negative breast cancer cells (MDA-MB-231) compared to non-cancer cells (HEK-293T). This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.