Nanoparticle-mediated IgE-receptor aggregation and signaling in RBL mast cells.
Nanoparticle-mediated IgE-receptor aggregation and signaling in RBL mast cells.
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DOI：
10.1021/ja907125t
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发表时间：
2009-12-02
影响因子：
15
通讯作者：
Tan, Weihong
中科院分区：
文献类型：
--
作者：
Huang, Yu-Fen;Liu, Haipeng;Xiong, Xiangling;Chen, Yan;Tan, Weihong
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。虽然有可能通过合成手段产生这种改变的信号转导，但效应物的化学定义的多价配体的开发有时是困难和繁琐的。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，我们直接解决这些挑战，展示了如何精确控制的平均直径的金纳米粒子（AuNPs）可以很容易地合成和表面改性与二硝基苯基（DNP）在一个同样良好控制的配体密度，或间距。我们发现，纳米颗粒的大小和表面配体密度在膜抗体-受体（IgE-FcεRI）结合和交联过程中起着关键的调节作用，这反过来又导致大鼠嗜碱性白血病细胞的脱粒和随后的化学介质释放。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活化。因此，这些结果表明，纳米颗粒不仅作为多价结合的简单平台，而且作为关键生物功能的介质。因此，我们在这里报告的研究结果可能会提供洞察使用纳米粒子作为一个全面的工具，用于详细的受体/配体相互作用的研究和设计的纳米级交付和治疗系统。
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-FcεRI) 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 not only serve 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.
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影响因子：
2.9
作者：
Das, Raibatak;Baird, Emily;Goldstein, Byron
通讯作者：
Goldstein, Byron
DOI：
10.1073/pnas.70.12.3305
发表时间：
1973-01-01
影响因子：
11.1
作者：
POLJAK, RJ;AMZEL, LM;SAUL, F
通讯作者：
SAUL, F
影响因子：
38.3
作者：
Jiang, Wen;Kim, Betty Y. S.;Chan, Warren C. W.
通讯作者：
Chan, Warren C. W.
DOI：
10.1002/chem.200802305
发表时间：
2009
期刊：
Chemistry (Weinheim an der Bergstrasse, Germany)
影响因子：
--
作者：
Chen Y;Munteanu AC;Huang YF;Phillips J;Zhu Z;Mavros M;Tan W
通讯作者：
Tan W
影响因子：
7.4
作者：
Chen, SJ;Chang, HT
通讯作者：
Chang, HT