<br>RBL 肥大细胞中纳米颗粒介导的 IgE 受体聚集和信号传导,Journal of the American Chemical Society

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RBL 肥大细胞中纳米颗粒介导的 IgE 受体聚集和信号传导
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2009-12-02 , DOI: 10.1021/ja907125t
Yu-Fen Huang ₁ , Haipeng Liu , Xiangling Xiong , Yan Chen , Weihong Tan

Affiliation

复杂的细胞行为通常由多价配体触发，多价配体首先与膜受体结合，然后促进受体聚集，从而改变细胞内信号转导。虽然可以通过合成手段产生这种改变的信号转导，但效应子的化学定义的多价配体的开发有时是困难且乏味的。具体来说，抗体内两个结合位点之间的平均间距和细胞膜上受体之间的平均距离通常大于大多数有机分子。在这项研究中，我们通过演示如何轻松合成平均直径精确控制的金纳米粒子（AuNP）并在同样控制良好的配体密度或间距下用二硝基苯基（DNP）进行表面修饰，从而直接解决这些挑战。我们发现纳米颗粒尺寸和表面配体密度在膜抗体受体（IgE-Fc epsilonRI）结合和交联过程中发挥着关键的调节作用，这反过来又导致大鼠脱粒和随后释放化学介质嗜碱性白血病细胞。此外，通过调整 DNP-AuNP 结构，我们发现我们的缀合物可以促进或抑制细胞激活。因此，这些结果表明纳米颗粒不仅可以作为多价结合的简单平台，而且可以作为关键生物功能的介质。因此，我们在此报告的研究结果可能有助于深入了解纳米颗粒作为综合工具的用途，用于详细的受体/配体相互作用研究以及纳米级递送和治疗系统的设计。

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Nanoparticle-Mediated IgE−Receptor Aggregation and Signaling in RBL Mast Cells

Complex cell behaviors are usually triggered by multivalent ligands that first bind to membrane receptors and then promote receptor clustering, thus altering intracellular signal transduction. While it is possible to produce such altered signal transduction by synthetic means, the development of chemically defined multivalent ligands of effectors is sometimes difficult and tedious. Specifically, the average spacing between two binding sites within an antibody and the average distance between receptors on the cell membrane are usually larger than most organic molecules. In this study, we directly address these challenges by demonstrating how gold nanoparticles (AuNPs) of precisely controlled mean diameters can be easily synthesized and surface-modified with dinitrophenyl (DNP) at an equally well-controlled ligand density or spacing. We found that both nanoparticle size and surface ligand density play key regulatory roles in the process of membrane antibody-receptor (IgE-Fc epsilonRI) binding and cross-linking, which, in turn, leads to degranulation and consequent release of chemical mediators on rat basophilic leukemia cells. In addition, by adjusting DNP-AuNP architecture, we discovered that our conjugates could either promote or inhibit cellular activation. Thus, these results demonstrate that nanoparticles serve not only as simple platforms for multivalent binding but also as mediators for key biological functions. As such, the findings we report here may provide insight into the use of nanoparticles as a comprehensive tool for use in detailed receptor/ligand interaction studies and in the design of nanoscale delivery and therapeutic systems.

更新日期：2009-12-02

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