College of Biological Sciences and Biotechnology, Beijing Forestry University, Beijing 100083, People's Republic of China.
Nanotechnology. 2017 Feb 24;28(8):085102. doi: 10.1088/1361-6528/aa56e0. Epub 2017 Jan 5.
The nanoparticles (NPs) functionalized with charged ligands are of particular significance due to their potential drug/gene delivery and biomedical applications. However, the molecular mechanism of endocytosis of the charged NPs by cells, especially the effect of the NP-NP and NP-biomembrane interactions on the internalization pathways is still poorly understood. In this work, we systematically investigate the internalization behaviors of the positively charged NPs by combining experiment technology and dissipative particle dynamics (DPD) simulation. We experimentally find an interesting but highly counterintuitive phenomenon, i.e. the multiple positively charged NPs prefer to enter cells cooperatively although the like-charged NPs have obvious electrostatic repulsion. Furthermore, we adopt the DPD simulation to confirm the experimental findings, and reveal that the mechanism of the cooperative endocytosis between like-charged NPs is definitely caused by the interplay of particle size, the charged ligand density on particle surface and local concentration of NPs. Importantly, we not only observe the normal cooperative endocytosis of like-charged NPs in cell biomembrane like neutral NP case, but also predict the 'bud' cooperative endocytosis of like-charged NPs which is absence in the neutral NP case. The results indicate that electrostatic repulsion between the positively charged nanoparticles plays an important role in the 'bud' cooperative endocytosis of like-charged NPs.
带电荷配体的纳米颗粒（NPs）由于其在药物/基因传递和生物医学应用方面的潜力而具有特别重要的意义。然而，带电荷的 NPs 被细胞内吞的分子机制，特别是 NP-NP 和 NP-生物膜相互作用对内吞途径的影响，仍然知之甚少。在这项工作中，我们通过实验技术和耗散粒子动力学（DPD）模拟相结合，系统地研究了带正电荷的 NPs 的内吞行为。我们实验发现了一个有趣但非常违反直觉的现象，即尽管带相同电荷的 NPs 之间存在明显的静电排斥，但多个带正电荷的 NPs 更倾向于协同进入细胞。此外，我们采用 DPD 模拟来证实实验结果，并揭示了带相同电荷的 NPs 之间协同内吞的机制，这肯定是由颗粒尺寸、颗粒表面带电配体密度和 NPs 的局部浓度相互作用引起的。重要的是，我们不仅在细胞生物膜中观察到了与中性 NP 情况相似的带相同电荷的 NPs 的正常协同内吞，而且还预测了带相同电荷的 NPs 中不存在的“芽”协同内吞。结果表明，带正电荷的纳米颗粒之间的静电排斥在带相同电荷的纳米颗粒的“芽”协同内吞中起着重要作用。
