Effect of Short PEG on Near-Infrared BODIPY-Based Activatable Optical Probes.

Targeted near-infrared (NIR) fluorescence probes are playing a significant role in biomedical imaging because NIR penetrates deeper into tissues and is associated with reduced autofluorescence compared to visible light fluorescence probes. Long-wavelength emitting 4,4-difluoro-4-bora-3a,4a-diaza--indacene (BODIPY) is an attractive platform for synthesizing NIR fluorophores because of its high photostability, high molar absorption coefficient, and sharp absorption and emission spectra. However, its lipophilicity hampers the conjugation chemistry necessary to add targeting moieties. In this study, we synthesized a novel NIR BODIPY derivative, . Substitutions of ethylene-bridged pyrrole units at the 3- or 5-position of the parent BODIPY chromophore result in a red shift of more than 200 nm. However, cannot be conjugated to antibodies because of its hydrophobicity. Therefore, we synthesized by adding short poly(ethylene glycol) to and successfully conjugated to cetuximab and trastuzumab. microscopic studies showed that conjugated antibodies were activated after internalization and lysosomal processing, which means that acts as an activatable probe only turning on after cellular internalization. After the administration of conjugated antibodies, mice tumors were detected with high tumor to background ratios for a long period. These results suggest that has potential as an activatable fluorescence probe for further clinical applications.