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Self-assembled nanostructures of amphiphilic peptides have a wide range of applications in bioimaging and delivery systems. In this study, we design and synthesize a biocompatible amphiphilic peptide (C-3) consisting of an RVRRFFF sequence and a nitrobenzoxadiazole fluorophore that can self-assemble into stable micelles for specifically detecting furin, a kind of proprotein convertase with promoting tumor progression. The self-assembly of C-3 with a β-sheet nanostructure is capable of a rapid and specific response to furin in only 5 min in aqueous solution because of the existence of the RVRR motif in the C-3 molecule. The C-3 nanostructures thus can selectively distinguish high furin-expressing cancer cells, like MDA-MB-231 cells, a kind of human breast cancer cells, from normal cells. Furthermore, the C-3 self-assembly can stay in living cells for a long time and are capable of durable detection of intracellular furin, being good for tracer analysis. To our knowledge, this is the first example of self-assembly of a soluble amphiphilic peptide that can selectively detect furin in high furin-expressing live cells.

Early detection of drug-induced acute kidney injury (AKI) is crucial for effective treatment and prevention of further injury. It remains challenging, however, because of the lack of activatable indicators with multimodality imaging capability that could increase the accuracy of diagnosis by mutual verification. Herein, we report an activatable probe, FDOCl-22, that enabled dual-modality detection of the early-stage drug-induced AKI. FDOCl-22 was completely soluble in water and highly sensitive to hypochlorous acid (HOCl). Dramatic increases of both near-infrared (NIR) emission and absorption were observed after reaction with HOCl. A correlation between HOCl concentration and drug-induced AKI was established using FDOCl-22 as a tool. As a consequence, the HOCl-activated probe was able to detect the early-stage drug-induced AKI by dual-modality imaging, irrespective of the drug stimulation time or dosage, by combining NIR fluorescence and photoacoustic imaging.

Detecting myeloperoxidase (MPO) activity in living organisms is important because MPO contributes to the pathogenesis of many diseases such as rheumatoid arthritis and other inflammatory diseases, artherosclerosis, neurodegenerative disease, and some cancers. However, rapid and effective methods for the detection of basal MPO activity in living systems have not yet been reported. Herein, we report a near-infrared (NIR) emissive "turn-on" probe FD-301 that can specifically bind to MPO and accurately measure MPO activity in living cells and in vivo via a rapid response to initial hypochlorous acid (HOCl), produced by MPO. Notably, FD-301 could detect the basal level of MPO activity in human promyelocytic leukemia cells (HL-60) and could discriminate between MPO high-expression and low-expression cells. Furthermore, FD-301 was successfully applied to in vivo imaging of MPO in MPO-dependent diseases, such as arthritis and inflammatory bowel disease.

It is important to detect hydrogen peroxide (H2O2) near mitochondrial DNA (mtDNA) because mtDNA is more prone to oxidative attack than nuclear DNA (nDNA). In this study, a mitochondria-targeted fluorescence probe, pep3-NP1, has been designed and synthesized. The probe contains a DNA-binding peptide, a H2O2 fluorescence reporter, and a positively charged red emissive styryl dye to facilitate accumulation in mitochondria. Due to groove binding of the peptide with DNA, the styryl dye of pep3-NP1 intercalated into the bases of DNA, leading to an increase in red fluorescence intensity (centered at 646 nm) and quantum yield. In this case, pep3-NP1 was a turn-on probe for labeling DNA. Subcellular locations of pep3-NP1 and MitoTracker suggested that pep3-NP1 mostly accumulated in the mitochondria of live cells. Namely, as an intracellular DNA marker, pep3-NP1 bound to mtDNA. In the presence of H2O2, pep3-NP1 emitted green fluorescence (centered at 555 nm). Thus, the ratio of green with red fluorescence of pep3-NP1 was suitable to reflect the change of the H2O2 level near mtDNA in living cells. The detecting limit for H2O2 was estimated at 2.9 and 5.0 μM in vitro and in cultured cells, respectively. The development of pep3-NP1 could help in studies to protect mtDNA from oxidative stress.