Aminopeptidase N Activatable Fluorescent Probe for Tracking Metastatic Cancer and Image-Guided Surgery via in Situ Spraying

Abstract

The recurrence of malignant tumors is mostly caused by incompleted surgical resection. Especially, it is difficult for surgeons to detect and accurately remove metastatic tumors by predominantly using visual examination and palpation owing to the lack of effective means to specifically distinguish the boundary range between normal and tumor tissues. Thus, the development of activated fluorescent probe with superior tumor-to-normal (T/N) tissue ratios is particularly urgent in clinics. In view of CD13/aminopeptidase N (APN) regarded as a cancer-specific biomarker, mediating with progression, invasion, and migration of malignant tumor, herein, we reported an APN-responsive fluorescent probe YH-APN and demonstrated its application to distinguish cancer cells. Through in situ spraying manner, fluorescent superior tumor-to-normal (T/N) tissue ratios (subcutaneous transplantation tumor, 13.86; hepatic metastasis, 4.42 and 6.25; splenic metastasis, 4.99) were achieved. More importantly, we have demonstrated the ability to image metastasis tumor tissue less than 1 mm in diameter, highlighting the potential for this probe to be used as a tool in surgical resection. This research may spur the use of enzyme-activatable fluorescent probes for the progress of tumor diagnosis and image-guided surgery (IGS).

Combining viscosity-restricted intramolecular motion and mitochondrial targeting leads to selective tumor visualization

“…6 This latter condition can be met by using near-infrared fluorescence covering the first therapeutic window (650-900 nm), where both absorbance, light scattering and autofluorescence are low. 7 Viscosity, as the single-most important factor in diffusioncontrol processes, plays a vital role in chemistry and biological activities. 8 In fact, unusual variations in micro-viscosity of cell is associated with many human-diseases, such as diabetes, Alzheimer's disease, atherosclerosis and especially, cell malignancy.…”

CD13 promotes hepatocellular carcinogenesis and sorafenib resistance by activating HDAC5‐LSD1‐NF‐κB oncogenic signaling

“…9 Aminopeptidase N (also named CD13) is a widely expressed type II membrane-bound metalloprotease involved in pleiotropic functions, such as cell adhesion, proliferation, and motility. 10 Recent research demonstrated that CD13 is a novel marker for semi-quiescent CSCs in HCC and is responsible for the chemoresistance. 11 Although CD13 may be a potential therapeutic target for alleviating drug resistance in HCC therapy, the potential role and underlying molecular regulation mechanism by which CD13 contributes to the sorafenib resistance remain poorly understood.…”

“…Recently studies reported the correlation between sorafenib resistance and tumor cell subpopulations with stem/progenitor cell phenotypes in HCC, implicating that targeting these subpopulations might be a promising option for overcoming drug resistance in HCC 9 . Aminopeptidase N (also named CD13) is a widely expressed type II membrane‐bound metalloprotease involved in pleiotropic functions, such as cell adhesion, proliferation, and motility 10 . Recent research demonstrated that CD13 is a novel marker for semi‐quiescent CSCs in HCC and is responsible for the chemoresistance 11 .…”

Most recent advances on enzyme‐activatable optical probes for bioimaging

“…Recently, activatable probes for the evaluation of the activity of APs, including leucine AP and aminopeptidase N (APN), have been reported. [ 101–104 ]…”