Synthesis And Applications Of Fluorescent Recognition Dyes Based On KIAA1363 Enzyme

According to Global Cancer Statistics reported by World Health Organization,the incidence trend of cancer was serious with obviously rising morbidity and mortality around the world.There were more than 50% of new cases in Asia and most of them were concentrated in China.Nowadays,traditional detection methods of cancer with expensive medical price,large radiation damage,low spatial resolution,and poor time efficiency have been unable to meet the current needs of detection of cancer.Therefore,it is significant to establish rapid,sensitive and simple methods for cancer identification.The reasonable combination of fluorescent technology and biomarker-targeting detection provided a powerful way to solve the problem of cancer detection.In this paper,basing on PET mechanism,two novel "off-on" fluorecent recognition dyes,NB-AX and NP-AX were desighed and synthesized based on the research of cancer biomarker serine hydrolase KIAA1363 and the specific recognition inhibitor AX11890 of KIAA1363.NB-AX was the first specific KIAA163-targeting near-infrared fluorescent probe.Upon addition of serine hydrolase KIAA1363,the fluorescence emission at 680 nm enhanced immediately,and increased linearly with the KIAA1363 concentration.The detection limit could be calculated as 0.58 ?g/ml(12.6 n?,3?/k).The low cytotoxicity,excellent selectivity as well as the near-infrared optical properties of NB-AX represented suitable features for bioinstrumentation.NB-AX was also able to ultrafast distinguish breast cancer cells from normal cells in fluorescent imaging(less than 1 min)and screen cancer cells vastly in flow cytometry.Noteworthy,NB-AX was effective to distinguish breast cancer tissues from adjacent tissues accurately in the same field of image and was able to label MDA-MB-231 xenografts tumors in vivo with lighting up KIAA1363 overexpressing tumor.NB-AX is an excellent candidate to find further application in diagnostic imaging and real time imaging of breast tumor in vivo and in situ.NP-AX was specific two-photon fluorescent recognition dyes with "off-on" response to serine hydrolase KIAA163 and was able to distinguish cancer cells from non-cancer cells via single-photon and two-photon fluorescent images.Particularly,NP-AX had excellent two-photon fluorescent imaging properties(two-photon excitation wavelength 800 nm)with higher sensitivity and higher signal-to-noise ratio than single-photon fluorescent imaging.Similarly,NP-AX can also be applied in flow cytometry for screening large amounts of cancer cells.