Department of Chemistry, University of California , Irvine, California 92697-2025, United States.
Institut für Chemie und Biochemie, Freie Universität Berlin , Takustrasse 3, 14195, Berlin, Germany.
Biomacromolecules. 2015 Dec 14;16(12):3869-77. doi: 10.1021/acs.biomac.5b01196. Epub 2015 Dec 1.
The development of safe and effective delivery vectors is a great challenge for the medicinal application of RNA interference (RNAi). In this study, we aimed to develop new synthetic transfection agents based on dendritic polyglycercol (dPG), which has shown great biocompatibility in several biomaterial applications. Histidine and aromatic amino acids were conjugated to the amine-terminated dPGs through amide bonds. We systematically tuned the amino acid combination, functionalization ratio, ligand density, and dPG core size to find optimal vectors. It was found that histidine-tryptophan-functionalized dPGs exhibited improved delivery efficiency and greatly reduced toxicity over simple amine-terminated dPGs. Furthermore, the optimized vectors exhibited strong siRNA binding and high transfection efficiency in serum containing media. The results indicate that the current amino acid-functionalized dPG system is a promising candidate for in vivo siRNA delivery applications.
安全有效的递药载体的开发是 RNA 干扰（RNAi）在医学应用上的一大挑战。在本研究中，我们旨在开发基于树枝状聚甘油（dPG）的新型合成转染试剂，dPG 在几种生物材料应用中已显示出极好的生物相容性。通过酰胺键将组氨酸和芳香族氨基酸连接到末端为胺基的 dPG 上。我们通过系统地调整氨基酸组合、功能化比例、配体密度和 dPG 核大小来寻找最佳载体。结果发现，组氨酸-色氨酸功能化的 dPG 与简单的末端为胺基的 dPG 相比，显示出更高的递送效率和大大降低的毒性。此外，优化后的载体在含血清的培养基中表现出强的 siRNA 结合和高的转染效率。结果表明，当前的氨基酸功能化 dPG 系统是体内 siRNA 递送应用的有前途的候选者。
