Ragon Institute of MGH, MIT, and Harvard, Cambridge , Massachusetts 02139 , United States.
Howard Hughes Medical Institute, Chevy Chase , Maryland 20815 , United States.
Bioconjug Chem. 2018 Apr 18;29(4):1131-1140. doi: 10.1021/acs.bioconjchem.7b00777. Epub 2018 Feb 27.
The development of synthetic nanomaterials that could embed within, penetrate, or induce fusion between membranes without permanent disruption would have great significance for biomedical applications. Here we describe structure-function relationships of highly water-soluble gold nanoparticles comprised of an ∼1.5-5 nm diameter metal core coated by an amphiphilic organic ligand shell, which exhibit membrane embedding and fusion activity mediated by the surface ligands. Using an environment-sensitive dye anchored within the ligand shell as a sensor of membrane embedding, we demonstrate that particles with core sizes of ∼2-3 nm are capable of embedding within and penetrating fluid bilayers. At the nanoscale, these particles also promote spontaneous fusion of liposomes or spontaneously embed within intact liposomal vesicles. These studies provide nanoparticle design and selection principles that could be used in drug delivery applications, as membrane stains, or for the creation of novel organic/inorganic nanomaterial self-assemblies.
合成纳米材料的发展,可以在不造成永久破坏的情况下嵌入、穿透或诱导膜之间的融合,这将对生物医学应用具有重要意义。在这里,我们描述了由直径约为 1.5-5nm 的金属核和由两亲性有机配体壳组成的高度水溶性金纳米粒子的结构-功能关系,其表面配体介导了膜嵌入和融合活性。我们使用作为膜嵌入传感器的锚固在配体壳内的环境敏感染料,证明了具有约 2-3nm 核大小的颗粒能够嵌入并穿透流体双层膜。在纳米尺度上,这些颗粒还促进脂质体的自发融合或自发嵌入完整的脂质体囊泡。这些研究为药物输送应用、膜染色剂或新型有机/无机纳米材料自组装体的创建提供了纳米颗粒设计和选择原则。