posted on 2020-03-31, 17:03authored byYibo Zhou, Sheng Yang, Jingru Guo, Hao Dong, Keyi Yin, Wei Tao Huang, Ronghua Yang
Accurate
and sensitive imaging of hypoxia associated with inflammatory
bowel disease (IBD) is significant for the precise diagnosis and treatment
of this disease, but it remains a challenge for traditional hypoxia-activatable
fluorescence probes because of a more moderate hypoxic state during
IBD than under other pathological conditions. To address this issue,
herein, we designed a hypoxia-activatable and cytoplasmic protein-powered
fluorescence cascade amplifier, named HCFA, to image hypoxia associated
with IBD in vivo. In our design, a 4-aminobenzoic
acid (azo)-modified mesoporous silica nanoparticle (MSN) was used
as a container to load black hole quencher 2 (BHQ2) and cytoplasmic
protein-binding squarylium dye (SQ); then, the β-cyclodextrin
polymer (β-CDP) combined with azo through a host–guest
interaction to form HCFA. Upon passive stagnation in the inflamed
tissue of IBD, the azo band would be cleaved under a hypoxic microenvironment,
and SQ was released to activate the fluorescence of HCFA. Moreover,
the unconstrained SQ can bind with cytoplasmic protein to exhibit
drastic fluorescence intensity enhancement, realizing the fluorescence
signal amplification for imaging of hypoxia. When one takes advantage
of the large load capacity of MSN and the unique property of SQ, HCFA
can sense oxygen levels in the range of 0% to 10%. Meanwhile, the
fluorescence imaging results demonstrate that HCFA can sensitively
distinguish different levels of cellular hypoxia and monitor the variations
of hypoxia in vivo, highlighting HCFA as a promising
tool for the detection of hypoxia associated with IBD.