使用与间充质干细胞识别的肽偶联的 PAMAM 树枝状大分子进行受体介导的基因传递。
Receptor-mediated gene delivery using PAMAM dendrimers conjugated with peptides recognized by mesenchymal stem cells.
机构信息
CQM-Centro de Quimica da Madeira, MMRG, Departamento de Quimica, Universidade da Madeira, Campus Universitario da Penteada, 9000-390 Funchal, Portugal.
出版信息
Mol Pharm. 2010 Jun 7;7(3):763-74. doi: 10.1021/mp9002877.
As mesenchymal stem cells (MSCs) can differentiate into multiple cell types, the delivery of exogenous genes to this type of cell can be an important tool in tissue regeneration and engineering. However transfection of MSCs using nonviral gene delivery vectors is difficult, the development of more efficient and safe DNA vehicles being necessary. Moreover, specific transfection of MSCs may be required to avoid unwanted side effects in other tissues. In this study, a novel family of gene delivery vectors based on poly(amidoamine) (PAMAM) dendrimers functionalized with peptides displaying high affinity toward MSCs was prepared. The vectors were characterized with respect to their ability to neutralize, bind and compact plasmid DNA (pDNA). The complexes formed between the vectors and pDNA were analyzed concerning their size, zeta-potential, capacity of being internalized by cells and transfection efficiency. These new vectors exhibited low cytotoxicity, receptor-mediated gene delivery into MSCs and transfection efficiencies superior to those presented by native dendrimers and by partially degraded dendrimers.
由于间充质干细胞(MSCs)可以分化为多种细胞类型,因此将外源性基因递送到这种细胞类型可以成为组织再生和工程的重要工具。然而,使用非病毒基因传递载体转染 MSCs 非常困难,因此需要开发更有效和更安全的 DNA 载体。此外,为了避免其他组织产生不必要的副作用,可能需要对 MSCs 进行特异性转染。在这项研究中,制备了基于聚(酰胺-胺)(PAMAM)树突状聚合物的新型基因传递载体家族,这些树突状聚合物通过与对 MSCs 具有高亲和力的肽进行功能化。对载体的中和、结合和压缩质粒 DNA(pDNA)的能力进行了表征。分析了载体与 pDNA 之间形成的复合物的大小、ζ-电位、被细胞内化的能力和转染效率。这些新型载体表现出低细胞毒性、受体介导的 MSC 基因传递和转染效率,优于天然树突状聚合物和部分降解的树突状聚合物。