title: Nanotechnology and cancer: improving real-time monitoring and staging of bladder cancer with multimodal mesoporous silica nanoparticles.
abstract: BACKGROUND
  Despite being one of the most common cancers, bladder cancer is largely inefficiently and inaccurately staged and monitored. Current imaging methods detect cancer only when it has reached "visible" size and has significantly disrupted the structure of the organ. By that time, thousands of cells will have proliferated and perhaps metastasized. Repeated biopsies and scans are necessary to determine the effect of therapy on cancer growth. In this report, we describe a novel approach based on multimodal nanoparticle contrast agent technology and its application to a preclinical animal model of bladder cancer. The innovation relies on the engineering core of mesoporous silica with specific scanning contrast properties and surface modification that include fluorescence and magnetic resonance imaging (MRI) contrast. The overall dimensions of the nano-device are preset at 80-180 nm, depending on composition with a pore size of 2 nm.
  
  
  METHODS
  To facilitate and expedite discoveries, we combined a well-known model of bladder cancer and our novel technology. We exposed nanoparticles to MB49 murine bladder cancer cells in vitro and found that 70 % of the cells were labeled by nanoparticles as measured by flow cytometry. The in vivo mouse model for bladder cancer is particularly well suited for T1- and T2-weighted MRI.
  
  
  RESULTS
  Under our experimental conditions, we demonstrate that the nanoparticles considerably improve tumor definition in terms of volumetric, intensity and structural characteristics. Important bladder tumor parameters can be ascertained, non-invasively, repetitively, and with great accuracy. Furthermore, since the particles are not biodegradable, repetitive injection is not required. This feature allows follow-up diagnostic evaluations during cancer treatment. Changes in MRI signals show that in situ uptake of free particles has predilection to tumor cells relative to normal bladder epithelium. The particle distribution within the tumors was corroborated by fluorescent microscopy of sections of excised bladders. In addition, MRI imaging revealed fibrous finger-like projections into the tumors where particles insinuated themselves deeply. This morphological characteristic was confirmed by fluorescence microscopy.
  
  
  CONCLUSIONS
  These findings may present new options for therapeutic intervention. Ultimately, the combination of real-time and repeated MRI evaluation of the tumors enhanced by nanoparticle contrast may have the potential for translation into human clinical studies for tumor staging, therapeutic monitoring, and drug delivery.
authors.affiliation: Department of Biomedical Engineering, University of Iowa, 1402 Seamans Center for the Engineering Arts and Sciences, Iowa City, IA 52242 USA ; NanoMedTrix, LLC, 2500 Crosspark Road, Suite E119, Coralville, IA 52241-4710 USA.
authors.forename: Sean K
authors.initials: SK
authors.lastname: Sweeney
authors.affiliation: Department of Urology, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, 3204 Medical Education Research Facility, 375 Newton Road, Iowa City, IA 52242 USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Urology, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, 200 Hawkins Dr., Iowa City, IA 52242 USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: O'Donnell
authors.affiliation: Department of Biomedical Engineering, University of Iowa, 1402 Seamans Center for the Engineering Arts and Sciences, Iowa City, IA 52242 USA ; NanoMedTrix, LLC, 2500 Crosspark Road, Suite E119, Coralville, IA 52241-4710 USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Assouline
keywords: Bladder; Cystoscopy; Magnetic resonance imaging; Mesoporous silica nanoparticles; Mouse orthotopic tumor model; Transitional cell carcinoma