Mitochondria-Targeted Fluorescent and Photoacoustic Imaging of Hydrogen Peroxide in Inflammation

Abstract

Hydrogen peroxide (H 2 O 2 ) is a prominent reactive oxygen species with relative stability, which makes it a potential diagnostic marker for pathological states. Excessive H 2 O 2 in mitochondria leads to oxidative stress and inflammation. However, precisely monitoring the level of H 2 O 2 at specific organelles (e.g., mitochondria) in vivo is still of urgent necessity. Therefore, we rationally designed a mitochondria-targeted near-infrared probe TPP-HCy-BOH for fluorescent/photoacoustic (FL/PA) dualmodal imaging of overproduced H 2 O 2 in an inflamed mouse model. TPP-HCy-BOH had a low LOD (0.348 μM), which is comparable to those of recently reported probes for H 2 O 2 detection. The high kinetic rate constant (k obs = 4.72 × 10 −3 s −1 ) of TPP-HCy-BOH toward H 2 O 2 is superior to recently reported H 2 O 2 probes. Compared to control probe HCy-BOH without the mitochondrial targeting moiety, TPP-HCy-BOH successfully images exogenous or endogenous H 2 O 2 in mitochondria with an additional 2.4-fold FL increase and 4.7-fold PA increase in HeLa cells or additional 2.1-fold FL increase and 3.3-fold PA increase in RAW 264.7 cells. In LPS-induced acute inflammation in vivo, TPP-HCy-BOH is more competent to image overproduced H 2 O 2 with additional 1.6-fold higher sensitivity of FL in abdomen and 2.0-fold higher sensitivity of PA in liver and longer retention time of 0.5 h than HCy-BOH. We anticipate that TPP-HCy-BOH could be employed for the FL/PA dual-modal diagnosis of pathological inflammation in clinic in near future.

Graphene foam/hydrogel scaffolds for regeneration of peripheral nerve using ADSCs in a diabetic mouse model

“…PNI could cause severe oxidative stress and inflammation, both of which have been demonstrated as negative factors for repairing PNI [53]. Meanwhile, persistent hyperglycemia could also induce oxidative stress and inflammation; thus, inhibition of oxidative stress and inflammation is significant in the repair of DPNI [54].…”

Recent Advances in Hydrogen Peroxide Responsive Organoborons for Biological and Biomedical Applications

“…Moreover, 29 a is superior to the control probe 29 b without a TPP moiety for imaging overproduced H 2 O 2 in lipopolysaccharide (2 mg mL À 1 )-induced acute inflammation in vivo with 1.6fold higher sensitivity of fluorescence in the abdominal tissue, two-fold higher sensitivity of photoacoustic signal in the liver, and 0.5 h longer retention time than 29 b. [66] As the toxicity of TPP is a concern for biological applications, other cation moiety such as quaternarized quinoline has been employed for targeting mitochondria (see 30-32). For example, the carbazole group conjugated with a quinoline quaternary ammonium salt and a boronate group forms 30 that can specifically localize in the mitochondria for rapid and convenient detection of H 2 O 2 in PMA-stimulated (1 μg mL À 1 ) HeLa cells.…”

“…The compound showed an LOD (limit of detection) of 0.348 μM and a rate constant of 4.72×10 −3 s −1 , and enabled both in vivo and ex vivo bioimaging of acute inflammation mouse models. Moreover, 29 a is superior to the control probe 29 b without a TPP moiety for imaging overproduced H 2 O 2 in lipopolysaccharide (2 mg mL −1 )‐induced acute inflammation in vivo with 1.6‐fold higher sensitivity of fluorescence in the abdominal tissue, two‐fold higher sensitivity of photoacoustic signal in the liver, and 0.5 h longer retention time than 29 b [66] . As the toxicity of TPP is a concern for biological applications, other cation moiety such as quaternarized quinoline has been employed for targeting mitochondria (see 30 – 32 ).…”

Recent Progress in Small‐Molecule Fluorescence and Photoacoustic Dual‐Modal Probes for the In‐Vivo Detection of Bioactive Molecules

“…Generally, the fluorescence and PA signals of probes are quenched by reason adjustment of spatial distance or structural transformations before reacting with the target. When the recognition site of the probe interacts specifically with bioactive molecules, the optical signal is restored by the formed new structure owing to the enhancement of the intramolecular charge transfer (ICT) mechanism, [27] or the hindrance of photon‐induced electron transfer [28] . Moreover, the obtained compounds commonly possess a remarkable NIR absorption signal and are suitable for PA imaging [25,29] .…”

“…Moreover, the tumor size and volume changes could be unambiguously observed by NIRF and PA dual‐modal imaging. Subsequently, Hai group also developed a NIRF and PA dual imaging probe, TPP‐HCy‐BOH, for the detection of mitochondrial H 2 O 2 levels in the inflamed mouse model [27] . Three parts involving the fluorophore (hemicyanine dye), the recognition group (boronic acid) and the mitochondrial‐targeting group (TPP) were connected by covalent bonds to construct the probe.…”