Department of Engineering Mechanics, School of Naval Architecture, Ocean and Civil Engineering (State Key Laboratory of Ocean Engineering, MOE Key Laboratory of Hydrodynamics), Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Nanoscale. 2019 Mar 7;11(9):4025-4034. doi: 10.1039/c8nr09381d. Epub 2019 Feb 15.
The cellular uptake of nanoparticles (NPs) has drawn significant attention due to their great importance and potential in drug delivery, bioimaging, and specific targeting. Here, we conduct a computational study on the translocation process of soft nanoparticles with different elasticities and surface hydrophobicities through a lipid bilayer membrane. It is shown that the translocation abilities of hydrophilic NPs can be enhanced by increasing their stiffness, while the penetrability of hydrophobic NPs is weakened by increasing the particle stiffness. The free energy analysis indicates that rigid hydrophilic NPs and soft hydrophobic NPs encounter lower energy barriers during penetration. In direct translocation, different deformation modes are observed for NPs with different surface hydrophobicities during cellular internalization. Further, deformation analysis demonstrates that hydrophilic NPs are flattened in the membrane plane, while hydrophobic NPs are elongated along the membrane norm during penetration. We conclude that the elasticity of NPs has an obvious impact on their ability to penetrate across the lipid bilayer membrane through different morphological responses of hydrophilic and hydrophobic NPs. These results shed light on the coupled effects of particle elasticity and surface hydrophobicity on the cellular uptake of elastic NPs, which may provide useful guidelines for designing effective nanocarrier systems for drug delivery.
由于纳米粒子（NPs）在药物传递、生物成像和特定靶向方面的重要性和潜力，其细胞摄取引起了广泛关注。在这里，我们通过脂质双层膜对具有不同弹性和表面疏水性的软纳米粒子的迁移过程进行了计算研究。结果表明，亲水性 NPs 的迁移能力可以通过增加其刚性来增强，而疏水性 NPs 的可穿透性则通过增加粒子刚性来减弱。自由能分析表明，刚性亲水性 NPs 和软疏水性 NPs 在穿透过程中遇到的能量障碍较低。在直接迁移中，对于具有不同表面疏水性的 NPs，在细胞内化过程中观察到不同的变形模式。此外，变形分析表明，亲水性 NPs 在膜平面上被压平，而疏水性 NPs 在穿透过程中沿膜法向被拉长。我们得出结论，NP 的弹性对其通过不同的亲水性和疏水性 NP 的形态响应穿透脂质双层膜的能力有明显影响。这些结果揭示了粒子弹性和表面疏水性对弹性 NP 细胞摄取的耦合效应，这可为设计有效的药物传递纳米载体系统提供有用的指导。
