Quantum dots facilitate simultaneous imaging and differentiation of multiple intratumoral species in vivo

Abstract

3851

Intravital microscopy allows us to study tumors with exquisite spatial resolution. However, key limitations with standard fluorophores hamper our ability to differentiate multiple components within the tumor mass from one another. Traditional fluorophores and fluorescent proteins are characterized by broad emission peaks. When imaging multiple probes, emission spectra overlap is therefore problematic. Further, traditional fluorophores photobleach with prolonged observation, reducing our ability to acquire temporal information. Colloidal semiconductor nanocrystals, or quantum dots, are fast emerging as a superior class of fluorescent probe; unlike their traditional counterparts, they resist photobleaching and may be tuned to a desired narrow emission spectrum. Despite these key advantages, the innate strengths of quantum dots for intravital tumor microscopy have yet to be explored. In this study, we illustrate with three examples how quantum dots may be used with intravital microscopy for in vivo cancer imaging. First, quantum dots are used to differentiate tumor vessels from signals due to both perivascular cells and components of the extravascular matrix. Second, the unique optical characteristics of quantum dots are used to screen the ability of a size-graded series of particulates to access the tumor mass. Last, quantum dots are used to monitor the homing of bone marrow derived precursor cells to the tumor. These diverse examples demonstrate the ability of quantum dots to uniquely tag multiple species within the tumor, and therefore facilitate both tumor pathophysiology and drug delivery studies.