Cambridge Advanced Imaging Centre, Dept. of Physiology, Development and Neuroscience, Anatomy Building, Cambridge University, Downing Street, Cambridge CB2 3DY, UK.
Biomaterials. 2014 Jan;35(3):1074-88. doi: 10.1016/j.biomaterials.2013.10.041. Epub 2013 Oct 30.
Agglomeration dramatically affects many aspects of nanoparticle-cell interactions. Here we show that hydroxyapatite nanoparticles formed large agglomerates in biological medium resulting in extensive particle uptake and dose-dependent cytotoxicity in human macrophages. Particle citration and/or the addition of the dispersant Darvan 7 dramatically reduced mean agglomerate sizes, the amount of particle uptake and concomitantly cytotoxicity. More surprisingly, agglomeration governed the mode of particle uptake. Agglomerates were sequestered within an extensive, interconnected membrane labyrinth open to the extracellular space. In spite of not being truly intracellular, imaging studies suggest particle degradation occurred within this surface-connected compartment (SCC). Agglomerate dispersion prevented the SCC from forming, but did not completely inhibit nanoparticle uptake by other mechanisms. The results of this study could be relevant to understanding particle-cell interactions during developmental mineral deposition, in ectopic calcification in disease, and during application of hydroxyapatite nanoparticle vectors in biomedicine.
团聚显著影响纳米颗粒与细胞相互作用的许多方面。在这里，我们表明，羟磷灰石纳米颗粒在生物介质中形成大的团聚体，导致人巨噬细胞大量摄取颗粒并产生剂量依赖性细胞毒性。颗粒的柠檬酸化和/或分散剂 Darvan 7 的添加显著降低了平均团聚体大小、颗粒摄取量以及随之而来的细胞毒性。更令人惊讶的是，团聚体控制了颗粒摄取的模式。团聚体被隔离在一个广泛的、相互连接的膜迷宫中，该迷宫与细胞外空间相通。尽管不是真正的细胞内，但成像研究表明，颗粒降解发生在这个与表面相连的隔室（SCC）中。团聚体的分散阻止了 SCC 的形成，但并没有完全通过其他机制抑制纳米颗粒的摄取。本研究的结果可能与理解发育性矿物质沉积、疾病中的异位钙化以及在生物医学中应用羟磷灰石纳米颗粒载体期间的颗粒-细胞相互作用有关。
