The effects of an RGD-PAMAM dendrimer conjugate in 3D spheroid culture on cell proliferation, expression and aggregation
The effects of an RGD-PAMAM dendrimer conjugate in 3D spheroid culture on cell proliferation, expression and aggregation
复制标题
3D 球体培养中 RGD-PAMAM 树枝状聚合物缀合物对细胞增殖、表达和聚集的影响
DOI：
10.1016/j.biomaterials.2013.01.003
复制
发表时间：
2013-04-01
期刊：
影响因子：
14
通讯作者：
Luo, Ying
中科院分区：
文献类型：
--
作者：
Jiang, Li-Yang;Lv, Bing;Luo, Ying
通过将生物分子配体以高密度呈现在表面上，配体修饰的树枝状聚合物能够以特异性和亲合力与膜受体和细胞结合。尽管有各种用途，配体-树枝状聚合物缀合物的基础研究主要集中在它们与细胞的结合行为，而它们在多细胞系统中的潜在生物活性和应用，特别是在三维（3D）培养系统中，仍然没有开发。在这项研究中，一个典型的粘附肽配体- RGD -被修饰为第4代聚酰胺胺（PAMAM），并研究了悬浮的RGD-PAMAM缀合物在多细胞球体培养的细胞上的生物活性。我们的结果表明，RGD-PAMAM缀合物，纳入后的三维球体，能够促进细胞增殖和聚集，并影响细胞外因子的mRNA表达的NIH 3 T3细胞。这些生物活性功能是多价依赖性的，因为没有观察到类似的效果为单价的RGD配体。我们的研究表明，多价配体-树枝状聚合物缀合物可以作为一种独特类型的人工因子来介导三维培养中的细胞微环境，这是一种归因于配体的空间组织和多价缀合物的可能的“细胞胶合”功能的性质。这一新发现为进一步探索多价配体-树枝状聚合物缀合物在3D细胞培养和组织工程中的应用打开了大门。(c)2013爱思唯尔有限公司保留所有权利。
By presenting biomolecular ligands on the surface in high density, ligand-decorated dendrimers are capable of binding to membrane receptors and cells with specificity and avidity. Despite the various uses, fundamental investigations on ligand-dendrimer conjugates have mainly focused on their binding behavior with cells, whereas their potential bioactivity and applications in multicellular systems, especially in three-dimensional (3D) culture systems, remains untapped. In this study, a typical adhesive peptide ligand - RGD - was modified to generation 4 polyamidoamine (PAMAM), and the bioactivity of suspended RGD-PAMAM conjugates was investigated on cells cultured as multicellular spheroids. Our results demonstrate that the RGD-PAMAM conjugates, after being incorporated into the 3D spheroids, were able to promote cellular proliferation and aggregation, and affect the mRNA expression of extracellular factors by NIH 3T3 cells. These bioactive functions were multivalency-dependent, as none of similar effects was observed for monovalent RGD ligand. Our study suggests that multivalent ligand-dendrimer conjugates may act as a unique type of artificial factors to mediate the cellular microenvironment in 3D culture, a property attributable to the spatial organization of the ligands and possible "cell-gluing" function of multivalent conjugates. This new finding opens the door for further exploring multivalent ligand-dendrimer conjugates for applications in 3D cell culture and tissue engineering. (c) 2013 Elsevier Ltd. All rights reserved.