title: Targeted multifunctional multimodal protein-shell microspheres as cancer imaging contrast agents.
abstract: OBJECTIVE
  In this study, protein-shell microspheres filled with a suspension of iron oxide nanoparticles in oil are demonstrated as multimodal contrast agents in magnetic resonance imaging (MRI), magnetomotive optical coherence tomography (MM-OCT), and ultrasound imaging. The development, characterization, and use of multifunctional multimodal microspheres are described for targeted contrast and therapeutic applications.
  
  
  METHODS
  A preclinical rat model was used to demonstrate the feasibility of the multimodal multifunctional microspheres as contrast agents in ultrasound, MM-OCT and MRI. Microspheres were functionalized with the RGD peptide ligand, which is targeted to α(v)β₃ integrin receptors that are over-expressed in tumors and atherosclerotic lesions.
  
  
  RESULTS
  These microspheres, which contain iron oxide nanoparticles in their cores, can be modulated externally using a magnetic field to create dynamic contrast in MM-OCT. With the presence of iron oxide nanoparticles, these agents also show significant negative T2 contrast in MRI. Using ultrasound B-mode imaging at a frequency of 30 MHz, a marked enhancement of scatter intensity from in vivo rat mammary tumor tissue was observed for these targeted protein microspheres.
  
  
  CONCLUSIONS
  Preliminary results demonstrate multimodal contrast-enhanced imaging of these functionalized microsphere agents with MRI, MM-OCT, ultrasound imaging, and fluorescence microscopy, including in vivo tracking of the dynamics of these microspheres in real-time using a high-frequency ultrasound imaging system. These targeted oil-filled protein microspheres with the capacity for high drug-delivery loads offer the potential for local delivery of lipophilic drugs under image guidance.
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 North Mathews Avenue, Urbana, IL 61801, USA.
authors.forename: Renu
authors.initials: R
authors.lastname: John
authors.forename: Freddy T
authors.initials: FT
authors.lastname: Nguyen
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Kolbeck
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Chaney
authors.forename: Marina
authors.initials: M
authors.lastname: Marjanovic
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Suslick
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Boppart
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000737:chemistry; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D045423:Microbubbles; D008863:Microspheres; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D039302:Integrin alphaVbeta3; D058185:Magnetite Nanoparticles; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid