Moghimi S M, Pavey K D, Hunter A C
Molecular Targeting and Polymer Toxicology Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, BN2 4GJ, Brighton, UK.
FEBS Lett. 2003 Jul 17;547(1-3):177-82. doi: 10.1016/s0014-5793(03)00707-5.
Intravenously injected polystyrene nanoparticles, which are prone to rapid sequestration by professional phagocytes, are converted to stealth entities by prior bolus intravenous injection of poloxamine 908. This behaviour is not due to alteration in macrophage phagocytic activity. Laser Doppler anemometry and surface plasmon resonance were used to unravel the mechanisms fundamental to generation of such stealth entities in vivo by poloxamine 908. Electrophoretic mobility of poloxamine pre-coated monodisperse polystyrene nanoparticles in serum, which behave as stealth entities in vivo, was similar to that of uncoated nanoparticles incubated in poloxamine pre-treated serum. This observation supported the notion that poloxamine in serum can modify the surface of nanoparticles with similar topography to that of stealth poloxamine pre-coated particles, i.e. with polyoxyethylene chains projected from the surface. Surface plasmon resonance optical phenomenon was used for real-time monitoring of protein-poloxamine interactions and adsorption at the polystyrene interface. It was found that poloxamine can not only adsorb to a serum-modified surface but in addition poloxamine in serum can form macromolecular complexes with high affinity for adsorption to a polystyrene lattice. A role for serum albumin in surface modification of nanoparticles by poloxamine 908 is also identified. Hence, our biophysical observations correlate precisely with the in vivo longevity of uncoated polystyrene nanoparticles in poloxamine pre-treated rats. This rational and sensitive biophysical approach has unravelled the probable mechanism fundamental to generation of stealth entities in vivo and therefore has application in the design and nano-engineering of stealth colloidal carriers for optimal biological performance.
静脉注射的聚苯乙烯纳米颗粒容易被专业吞噬细胞迅速隔离，通过预先大剂量静脉注射泊洛沙明908可将其转化为隐形实体。这种行为并非由于巨噬细胞吞噬活性的改变。使用激光多普勒血流仪和表面等离子体共振来揭示泊洛沙明908在体内产生此类隐形实体的基本机制。在血清中，预先用泊洛沙明包被的单分散聚苯乙烯纳米颗粒（在体内表现为隐形实体）的电泳迁移率与在经泊洛沙明预处理的血清中孵育的未包被纳米颗粒相似。这一观察结果支持了血清中的泊洛沙明可以修饰纳米颗粒表面的观点，其拓扑结构与隐形泊洛沙明预包被颗粒相似，即表面伸出聚氧乙烯链。表面等离子体共振光学现象用于实时监测蛋白质与泊洛沙明在聚苯乙烯界面的相互作用和吸附。研究发现，泊洛沙明不仅可以吸附到血清修饰的表面，而且血清中的泊洛沙明还可以形成对聚苯乙烯晶格具有高吸附亲和力的大分子复合物。还确定了血清白蛋白在泊洛沙明908对纳米颗粒表面修饰中的作用。因此，我们的生物物理观察结果与未包被的聚苯乙烯纳米颗粒在经泊洛沙明预处理的大鼠体内的寿命精确相关。这种合理且灵敏的生物物理方法揭示了体内产生隐形实体的可能基本机制，因此在设计和纳米工程隐形胶体载体以实现最佳生物学性能方面具有应用价值。
