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

Abstract

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 λ_ex = 660 nm and λ_em = 710 nm, while it turned into another fluorescent Aza-BODIPY dye (BOD) with strong NIR fluorescence at λ_ex = 720 nm and λ_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.