Abstract
Optical imaging, which uses neither ionizing radiation (as in X-ray computed tomography) nor radioactive materials (as in positron emission tomography or single photon emission computed tomography),([1]) has emerged as a powerful imaging modality during the last two decades.([2]) Optical imaging has been widely employed for oncological and other applications due to its ability to noninvasively differentiate between diseased (e.g., tumor) and healthy tissues based on differential dye accumulations.([3]) The need for relatively high (up to ~µM) concentrations of dyes in optical imaging, however, limits its application in many areas, such as detecting low concentrations of biological targets. For example, many biomarkers are overexpressed in the nM concentrations in diseased tissues,([4]) and cannot be readily visualized by optical imaging. Dye-loaded nanoparticles represent a logical solution to lowering the detection limit due to their ability to carry a large payload of dye molecules as well as to target certain cell types by conjugation to affinity molecules. Luminescent quantum dots have indeed been extensively explored as bright and stable contrast agents for optical imaging.([5]) The non-degradable nature of and the use of toxic elements in many quantum dot formulations however limit their applications in many areas. Most of fluorescent dye molecules, on the other hand, have small Stokes shifts and tend to have a significant overlap between absorption and fluorescent emission spectra. As a result, these fluorescence dyes will suffer from severe self-quenching if they are brought into close proximity with each other, as in nanoparticles with high dye loadings.