School of Chemistry and Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Biomacromolecules. 2011 Apr 11;12(4):1339-48. doi: 10.1021/bm200116z. Epub 2011 Mar 8.
We synthesized a library of polymer-coated gold nanoparticles (AuNPs) with well-defined sizes (5, 10, and 20 nm) and surface properties, and investigated their efficiency to cross the Caco-2 epithelial barrier and disrupt tight junctions connecting the cellular barrier. The positively charged and hydrophobic polymer-coated AuNPs showed little or no translocation across the model Caco-2 monolayer. Most of these positive and hydrophobic nanoparticles were either bound to the surface or internalized within the cell. The neutral and negatively charged polymer-coated AuNPs with a size of 5 nm showed a significantly higher translocation. All polymer-coated AuNPs induced the translocation of small molecules across the cellular monolayer, suggesting the loosening of the paracellular tight junction joining individual cells. The decrease in the TEER values of the monolayers supported the opening of the tight junctions. These tight junctions fully recovered for most polymer-coated AuNPs 12 h after removal of the nanoparticles. The exception was the cationic polymer-coated AuNPs in which the barrier function only recovered up to 62%. The library of polymer-coated AuNPs showed no apparent signs of hemolysis to erythrocytes at physiological pH. Our investigation has provided insight on the influence of polymer coatings on the epithelial barrier.
我们合成了一系列具有明确尺寸（5、10 和 20nm）和表面性质的聚合物包覆金纳米粒子（AuNPs），并研究了它们穿过 Caco-2 上皮屏障和破坏连接细胞屏障的紧密连接的效率。带正电荷和疏水性聚合物包覆的 AuNPs 穿过模型 Caco-2 单层的转运效率很低或没有。这些带正电荷和疏水性的大多数纳米粒子要么与表面结合，要么被细胞内化。带负电荷的中性和带正电荷的聚合物包覆的 5nm AuNPs 显示出明显更高的转运效率。所有聚合物包覆的 AuNPs 均诱导小分子穿过细胞单层转运，表明细胞间紧密连接的松弛。单层的 TEER 值降低支持紧密连接的打开。在去除纳米粒子 12 小时后，大多数聚合物包覆的 AuNPs 的紧密连接完全恢复。阳离子聚合物包覆的 AuNPs 除外，其屏障功能仅恢复至 62%。聚合物包覆的 AuNPs 库在生理 pH 值下对红细胞没有明显的溶血迹象。我们的研究深入了解了聚合物涂层对上皮屏障的影响。
