Obesity is a major risk factor for diabetes, heart disease and other health problems. Adipose tissue plays a central role in the development of obesity and obesity-associated diseases. Gene therapy targeting adipose tissue may provide a promising strategy for obesity treatment. However, nucleic acid delivery to adipose tissue or even cultured adipocytes is challenging due to low delivery efficacy and high toxicity of the current cationic lipid based delivery systems, or monoamphiphiles. Herein, we report using dendritic peptide bolaamphiphiles (bolas) to deliver siRNA to primary adipocytes and hepatocytes. The bola consists of two l-Lysine dendrons connected to a fluorocarbon core through disulfide linkages. The Lysine dendrons are functionalized with l-histidine and l-tryptophan to promote endosomal escape and cellular uptake. The bola exhibited over 70% knockdown of GAPDH gene in both primary adipocytes and hepatocytes. Importantly, different from Lipofectamine that significantly reduced genes involved in lipolysis, lipogenesis, fatty acid oxidation and ketogenesis, the bolas had little to no effect on these genes. These results demonstrate the bola as a promising new vector for clinical and experimental applications for delivery of siRNA to metabolic organs.

肥胖是糖尿病，心脏病和其他健康问题的主要危险因素。脂肪组织在肥胖症和肥胖症相关疾病的发展中起着核心作用。针对脂肪组织的基因治疗可能为肥胖症治疗提供有前途的策略。然而，由于目前基于阳离子脂质的递送系统或单两亲物的低递送功效和高毒性，将核酸递送至脂肪组织或什至培养的脂肪细胞是具有挑战性的。在本文中，我们报道了使用树突状肽类双亲亲属（bolas）将siRNA传递至初级脂肪细胞和肝细胞。叶片由两个通过二硫键连接到碳氟化合物核上的1-赖氨酸树突组成。这赖氨酸树突被1-组氨酸和1-色氨酸官能化以促进内体逃逸和细胞摄取。在原代脂肪细胞和肝细胞中，该小肠均表现出超过70％的GAPDH基因敲低。重要的是，与脂转染胺显着减少涉及脂肪分解，脂肪生成，脂肪酸氧化和生酮作用的基因不同，硼酸钾对这些基因几乎没有影响。这些结果表明，bola是有希望的新载体，可用于将siRNA传递至代谢器官的临床和实验应用。