Elasticity of Nanopartides Influences Their Blood Circulation, Phagocytosis, Endocytosis, and Targeting
Elasticity of Nanopartides Influences Their Blood Circulation, Phagocytosis, Endocytosis, and Targeting
复制标题
DOI：
10.1021/acsnano.5b00147
复制
发表时间：
2015-03-01
期刊：
影响因子：
17.1
通讯作者：
Mitragotri, Samir
中科院分区：
文献类型：
--
作者：
Anselmo, Aaron C.;Zhang, Mengwen;Mitragotri, Samir
纳米粒子的物理和化学修饰对其生物学功能的影响已被系统地研究和开发，以改善其循环和靶向。然而，纳米颗粒的柔性（即，弹性模量）对它们功能的影响已经在小得多的程度上进行了探索，并且调节纳米颗粒弹性的潜在益处还不清楚。在这里，我们描述了一种方法来合成聚乙二醇（PEG）为基础的水凝胶纳米粒子的均匀尺寸（200 nm）的弹性模量范围从0.255至3000 kPa。这些颗粒用于研究颗粒弹性对关键功能的作用，包括血液循环时间、生物分布、抗体介导的靶向作用、内吞作用和吞噬作用。我们的研究结果表明，较软的纳米粒子（10千帕）提供增强的循环，随后增强靶向相比，较硬的纳米粒子（3000千帕）在体内。此外，体外实验表明，较软的纳米颗粒在免疫细胞（J774巨噬细胞）、内皮细胞（bEnd.3）和癌细胞（4T1）中表现出显著降低的细胞摄取。调整纳米颗粒弹性可能提供了一种方法，通过提供增强的循环，减少免疫系统摄取和改善靶向来改善纳米颗粒的生物命运。
The impact of physical and chemical modifications of nanoparticles on their biological function has been systemically investigated and exploited to improve their circulation and targeting. However, the impact of nanoparticles' flexibility (i.e., elastic modulus) on their function has been explored to a far lesser extent, and the potential benefits of tuning nanoparticle elasticity are not clear. Here, we describe a method to synthesize polyethylene glycol (PEG)-based hydrogel nanoparticles of uniform size (200 nm) with elastic moduli ranging from 0.255 to 3000 kPa. These particles are used to investigate the role of particle elasticity on key functions including blood circulation time, biodistribution, antibody-mediated targeting, endocytosis, and phagocytosis. Our results demonstrate that softer nanoparticles (10 kPa) offer enhanced circulation and subsequently enhanced targeting compared to harder nanoparticles (3000 kPa) in vivo. Furthermore, in vitro experiments show that softer nanoparticles exhibit significantly reduced cellular uptake in immune cells (J774 macrophages), endothelial cells (bEnd.3), and cancer cells (4T1). Tuning nanoparticle elasticity potentially offers a method to improve the biological fate of nanoparticles by offering enhanced circulation, reduced immune system uptake, and improved targeting.