Koshkina Olga, Lajoinie Guillaume, Bombelli Francesca Baldelli, Swider Edyta, Cruz Luis J, White Paul B, Schweins Ralf, Dolen Yusuf, van Dinther Eric A W, van Riessen N Koen, Rogers Sarah E, Fokkink Remco, Voets Ilja K, van Eck Ernst R H, Heerschap Arend, Versluis Michel, de Korte Chris L, Figdor Carl G, de Vries I Jolanda M, Srinivas Mangala
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences (RIMLS), Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands; Physical Chemistry of Polymers, Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
Physics of Fluids Group, Technical Medical (TechMed) Centre and MESA+ Institute for, Nanotechnology, University of Twente, Drienerlolaan 5, 7522 NB, Enschede, The Netherlands.
Adv Funct Mater. 2019 May 9;29(19). doi: 10.1002/adfm.201806485. Epub 2019 Mar 13.
Ultrasound is the most commonly used clinical imaging modality. However, in applications requiring cell-labeling, the large size and short active lifetime of ultrasound contrast agents limit their longitudinal use. Here, 100 nm radius, clinically applicable, polymeric nanoparticles containing a liquid perfluorocarbon, which enhance ultrasound contrast during repeated ultrasound imaging over the course of at least 48 h, are described. The perfluorocarbon enables monitoring the nanoparticles with quantitative F magnetic resonance imaging, making these particles effective multimodal imaging agents. Unlike typical core-shell perfluorocarbon-based ultrasound contrast agents, these nanoparticles have an atypical fractal internal structure. The nonvaporizing highly hydrophobic perfluorocarbon forms multiple cores within the polymeric matrix and is, surprisingly, hydrated with water, as determined from small-angle neutron scattering and nuclear magnetic resonance spectroscopy. Finally, the nanoparticles are used to image therapeutic dendritic cells with ultrasound in vivo, as well as with F MRI and fluorescence imaging, demonstrating their potential for long-term in vivo multimodal imaging.
超声是最常用的临床成像方式。然而,在需要细胞标记的应用中,超声造影剂的大尺寸和短活性寿命限制了它们的长期使用。在此,描述了半径为100纳米、临床适用的、含有液态全氟碳的聚合物纳米颗粒,其在至少48小时的重复超声成像过程中增强超声造影。全氟碳能够通过定量氟磁共振成像监测纳米颗粒,使这些颗粒成为有效的多模态成像剂。与典型的核壳型基于全氟碳的超声造影剂不同,这些纳米颗粒具有非典型的分形内部结构。通过小角中子散射和核磁共振光谱测定,不蒸发的高度疏水全氟碳在聚合物基质内形成多个核心,并且令人惊讶地被水合。最后,这些纳米颗粒用于在体内用超声以及氟磁共振成像和荧光成像对治疗性树突状细胞进行成像,证明了它们在体内长期多模态成像的潜力。