title: Sol-gel synthesis and electrospraying of biodegradable (P2O5)55-(CaO)30-(Na2O)15 glass nanospheres as a transient contrast agent for ultrasound stem cell imaging.
abstract: Ultrasound imaging is a powerful tool in medicine because of the millisecond temporal resolution and submillimeter spatial resolution of acoustic imaging. However, the current generation of acoustic contrast agents is primarily limited to vascular targets due to their large size. Nanosize particles have the potential to be used as a contrast agent for ultrasound molecular imaging. Silica-based nanoparticles have shown promise here; however, their slow degradation rate may limit their applications as a contrast agent. Phosphate-based glasses are an attractive alternative with controllable degradation rate and easily metabolized degradation components in the body. In this study, biodegradable P2O5-CaO-Na2O phosphate-based glass nanospheres (PGNs) were synthesized and characterized as contrast agents for ultrasound imaging. The structure of the PGNs was characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), (31)P magic angle spinning nuclear magnetic resonance ((31)P MAS NMR), and Fourier transform infrared (FTIR) spectroscopy. The SEM images indicated a spherical shape with a diameter size range of 200-500 nm. The XRD, (31)P NMR, and FTIR results revealed the amorphous and glassy nature of PGNs that consisted of mainly Q(1) and Q(2) phosphate units. We used this contrast to label mesenchymal stem cells and determined in vitro and in vivo detection limits of 5 and 9 μg/mL, respectively. Cell counts down to 4000 could be measured with ultrasound imaging with no cytoxicity at doses needed for imaging. Importantly, ion-release studies confirmed these PGNs biodegrade into aqueous media with degradation products that can be easily metabolized in the body.
authors.affiliation: Division of Biomaterials and Tissue Engineering/Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8LD, UK.|Department of Chemistry/Faculty of Math and Physical Science, University College London, 20 Gordon Street, London WC1H 0AJ, UK.
authors.forename: Farzad
authors.initials: F
authors.lastname: Foroutan
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University, 318 Campus Drive, Stanford, CA 94305-5427, United States.
authors.forename: Jesse V
authors.initials: JV
authors.lastname: Jokerst
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University, 318 Campus Drive, Stanford, CA 94305-5427, United States.
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University, 318 Campus Drive, Stanford, CA 94305-5427, United States.
authors.forename: Ophir
authors.initials: O
authors.lastname: Vermesh
authors.affiliation: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Cheonan, 330-714, Dankook University, Republic of Korea.|Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 330- 714, Republic of Korea.|Department of Nanobiomedical Science and WCU Research Centre of Nanobiomedical Science, Dankook University, Chungnam 330-714, Republic of Korea.
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Division of Biomaterials and Tissue Engineering/Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8LD, UK.|Department of Nanobiomedical Science and WCU Research Centre of Nanobiomedical Science, Dankook University, Chungnam 330-714, Republic of Korea.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Knowles
mesh_terms: D017610:Calcium Compounds / Q000737:chemistry; D002470:Cell Survival; D060326:Chemistry Techniques, Synthetic; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism; D004560:Electricity; D005898:Glass / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000000981:diagnostic imaging* / Q000378:metabolism; D054118:Nanospheres / Q000737:chemistry* / Q000378:metabolism; D036103:Nanotechnology / Q000379:methods*; D010087:Oxides / Q000737:chemistry* / Q000378:metabolism; D017553:Phosphorus Compounds / Q000737:chemistry; D017670:Sodium Compounds / Q000737:chemistry; D013696:Temperature; D014463:Ultrasonography
chemical_list: D017610:Calcium Compounds; D003287:Contrast Media; D010087:Oxides; D017553:Phosphorus Compounds; D017670:Sodium Compounds; C096707:sodium oxide; C012500:phosphorus pentoxide; C016538:lime
keywords: electrospraying; phosphate-based glasses; sol−gel; ultrasound imaging