title: Exosome-like silica nanoparticles: a novel ultrasound contrast agent for stem cell imaging.
abstract: Ultrasound is critical in many areas of medicine including obstetrics, oncology, and cardiology with emerging applications in regenerative medicine. However, one critical limitation of ultrasound is the low contrast of target tissue over background. Here, we describe a novel cup-shaped silica nanoparticle that is reminiscent of exosomes and that has significant ultrasound impedance mismatch for labelling stem cells for regenerative medicine imaging. These exosome-like silica nanoparticles (ELS) were created through emulsion templating and the silica precursors bis(triethoxysilyl)ethane (BTSE) and bis(3-trimethoxysilyl-propyl)amine (TSPA). We found that 40% TSPA resulted in the exosome like-morphology and a positive charge suitable for labelling mesenchymal stem cells. We then compared this novel structure to other silica structures used in ultrasound including Stober silica nanoparticles (SSN), MCM-41 mesoporous silica nanoparticles (MSN), and mesocellular foam silica nanoparticles (MCF) and found that the ELS offered enhanced stem cell signal due to its positive charge to facilitate cell uptake as well as inherently increased echogenicity. The in vivo detection limits were <500 cells with no detectable toxicity at the concentrations used for labelling. This novel structure may eventually find utility in applications beyond imaging requiring an exosome-like shape including drug delivery.
authors.affiliation: Department of NanoEngineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0448, USA. jjokerst@ucsd.edu.
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Ma
authors.forename: Junxin
authors.initials: J
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Shi-Xiong
authors.initials: SX
authors.lastname: Chern
authors.forename: Eric Ruike
authors.initials: ER
authors.lastname: Zhao
authors.forename: Anamik
authors.initials: A
authors.lastname: Jhunjhunwala
authors.forename: Sean
authors.initials: S
authors.lastname: Darmadi
authors.forename: Hangrong
authors.initials: H
authors.lastname: Chen
authors.forename: Jesse V
authors.initials: JV
authors.lastname: Jokerst
mesh_terms: D000818:Animals; D003287:Contrast Media; D016503:Drug Delivery Systems; D055354:Exosomes; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008819:Mice, Nude; D008854:Microscopy, Electron; D053758:Nanoparticles; D016062:Porosity; D012822:Silicon Dioxide; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D012822:Silicon Dioxide