Conventional fluorescence imaging strategies rely on imaging agents that are “always on”, emitting constant signal regardless of their proximity or interaction with target tissues, cells, or markers of disease. As a result, the large volume of nonspecific signal makes the tissue or anatomical feature of interest more difficult to distinguish. Optical contrast agents whose fluorescence properties may be switched from OFF to ON in response to specific biological stimuli could minimize background signal and thus improve sensitivity and specificity. Herein, we report the development of an activatable fluorescence imaging agent capable of detecting hydrogen peroxide (H2O2) and acidic microenvironments, two important biomarkers shared by numerous diseases and inflammatory conditions (e.g. tumors, rheumatoid arthritis, atherosclerosis). This imaging agent consists of H2O2- and acid-responsive polymeric particles packed with a high concentration of near infrared (NIR) dyes. The close proximity of the dye molecules quenches their fluorescence, thus creating an “off-state“ The signal of this agent is “turned on” through the cleavage of protecting moieties on the polymer backbones upon exposure to either H2O2 or acidic pH, which reveals hydroxyl groups and thus increases the material’s hydrophilicity. Upon this solubility switch, dye molecules diffuse out of the polymer matrix, relieving the particle from intense fluorescence quenching (“on-state”). We have demonstrated the activation of our agent in three in vivo models: serum transfer-induced arthritis, carrageenan-induced paw inflammation, and breast tumor. In all three mouse models, regions of inflammation exhibit a unique fluorescence signal amplification mechanism, which enable detection of inflamed areas with target-to-background ratios reaching as high as 22, only 3 h post-injection. These results suggest that our novel activatable bioimaging agent could be applied to detect inflammation in vivo for clinical diagnosis of inflammatory conditions or to assess inflammation in various animal models.

Detecting inflammation in vivo using NIR activatable fluorescence imaging

251st National Meeting (2016)

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