title: Conditionally activating optical contrast agent with enhanced sensitivity via gold nanoparticle plasmon energy transfer: feasibility study.
abstract: BACKGROUND
  Molecular sensing/imaging utilizing fluorophores has been one of the most frequently used techniques in biomedical research. As for any molecular imaging techniques, fluorescence mediated sensing always seeks for greater specificity and sensitivity. Since fluorophores emit fluorescence while their electron energy state changes, manipulating the local electromagnetic field around the fluorophores may be a way to enhance the specificity and sensitivity. Gold nanoparticles (GNPs) are known to form a very strong electromagnetic field on their surface [i.e., surface plasmon field (SPF)], upon receiving photonic energy. The level of fluorescence change by GNP-SPF may range from complete quenching to extensive enhancement, depending upon the SPF strength, excitation and emission wavelengths, and quantum yield of the fluorophore.
  
  
  METHODS
  Here, we report a novel design that utilizes BOTH fluorescence quenching and enhancement abilities of the GNP in one single nano-entity, providing high specificity and sensitivity. The construct utilizes a specially designed molecular dual-spacer that places the fluorphore at the location with an appropriate GNP-SFP strength before and after exposed to the biomarker. A model system to test the concept was an optical signal mediator activated by urokinase-type plasminogen activator (uPA; breast cancer secreting enzyme).
  
  
  RESULTS
  The resulting contrast agent shows less than 10% of the natural fluorescence but, in the presence of uPA, its fluorescence emission is triggered and emits its fluorescence approximately twice of the natural form.
  
  
  CONCLUSIONS
  This study demonstrated that our novel design of an optical contrast agent can be conditionally activated with enhanced sensitivity, using both quenching and enhancement phenomena of fluorophores in the electromagnetic field of the appropriate strengths (in this case, locally generated by the GNP-SPF). This entity is similar to molecular beacon in terms of specificity but with greater sensitivity. In addition, it is not restricted to only DNA or RNA sensing but for any designs that cause the change in the distance between the fluorophore and GNP, upon the time of encountering biomarker of interest.
authors.affiliation: Department of Chemical Engineering, University of Louisville, Louisville, KY, 40292, USA. kyung.kang@louisville.edu.
authors.forename: Kyung Aih
authors.initials: KA
authors.lastname: Kang
authors.affiliation: Department of Chemical Engineering, University of Louisville, Louisville, KY, 40292, USA. Jianting.Wang@fda.hhs.gov.|Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Maryland, 20993, USA. Jianting.Wang@fda.hhs.gov.
authors.forename: Jianting
authors.initials: J
authors.lastname: Wang
mesh_terms: D015415:Biomarkers / Q000032:analysis; D003287:Contrast Media / Q000737:chemistry*; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry; D006046:Gold; D007211:Indoles / Q000737:chemistry; D053768:Metal Nanoparticles / Q000737:chemistry*; D057054:Molecular Imaging / Q000295:instrumentation / Q000379:methods*; D015394:Molecular Structure; D055095:Optics and Photonics / Q000379:methods; D011422:Propionates / Q000737:chemistry; D012680:Sensitivity and Specificity; D020349:Surface Plasmon Resonance; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D015415:Biomarkers; D003287:Contrast Media; C000604523:Cypate; D005456:Fluorescent Dyes; D007211:Indoles; D011422:Propionates; D006046:Gold; D014568:Urokinase-Type Plasminogen Activator