A dual-channel fluorescent ratio probe with hypoxia targeting and hypoxia activation capacity for tumour imaging

Efficient hypoxia diagnosis is a great challenge for nearly all solid tumours due to operability, permeability and specificity. Although some inspiring approaches have been explored to date, it is the first time that a dual-channel NIR probe (denoted as OPDEA/BOD-NO2) simultaneously with hypoxia targeting and activation capacity was employed to realize effective prolonged hypoxia ratio imaging in the present work. OPDEA/BOD-NO2 consists of hypoxia-targeting tertiary amine N-oxide based polymers and nitrobenzene modified Aza-BODIPY (BOD-NO2). OPDEA/BOD-NO2 had strong red fluorescence at lambda(ex) = 660 nm and lambda(em) = 710 nm, while it turned into another fluorescent Aza-BODIPY dye (BOD) with strong NIR fluorescence at Rex = 720 nm and A em = 790 nm in hypoxia microenvironment, providing two channels with big Stokes shift for hypoxia ratio imaging and monitoring probe distribution and activation, respectively. Meanwhile, hypoxia-targeting tertiary amine N-oxide based polymers could effectively enhance tumour accumulation (2.99-fold, 660 nm; and 2.74-fold, 720 nm) for prolonged hypoxia ratio imaging with obviously improved signal-to-background ratio within 48 hours, which is much better than that of PEG/BOD-NO2.

Automated summary

This study for the first time employed a dual-channel NIR probe for effective prolonged hypoxia ratio imaging. The probe had hypoxia targeting and activation capacity, allowing monitoring of probe distribution and activation in the hypoxic tumor microenvironment.