Construction Of Self-propelled Janus Short Fibers For Detection Of Circulating Tumor Cells

Cancer is one of the most devastating diseases in the world,killing millions every year.The scary aspect of cancer is the metastasis of cancer cells that can cause up to 90%of cancer-related deaths.Metastasis is the escape of tumor cells from the primary tumor site through the bloodstream and the formation of metastatic tumor colonies at the second site.This kind of cancer cells with stem cell characteristics that circulate in the peripheral blood and cause cancer metastasis are called circulating tumor cells.The incubation period of cancer is usually more than 10 years.Patients undergoing regular screening,early diagnosis,and early intervention will be able to receive treatment sooner so as to avoid the development of cancer until the middle and late stage.Therefore,the detection of circulating tumor cells in peripheral blood has extremely important clinical significance in the early screening of tumors,clinical treatment effects and prognostic evaluation.In the current study,Janus fibers were prepared by“side-by-side”electrospinning method with poly?styrene-maleic anhydride?copolymers on one side and poly?styrene-maleic anhydride?-1,6-Hexanediamine copolymers on the other side.Janus short fibers with different length-diameter ratio were prepared by the frozen section technique.In order to increase the interaction between the fluorescent probe and the target,the amino-modified TLS11a aptamer was modified to one side of the fiber by an amide reaction,and the catalase was immobilized to the fiber by polyetherimide and glutaraldehyde on the other side.Enzyme-and aptamer-modified Janus short fibers were obtained,and the immobilization of the enzyme and the movement of the Janus short fibers were studied.It was found that the immobilized enzyme has a higher activity under different conditions and the mean square displacement?MSD?is the largest for Janus short fibers with 10?mlong,and the fluorescence response is the best.By grafting thymidine to tetraphenylethylene,a fluorescent derivative of TPE-T was obtained,and guanine was grafted onto fluorescein isothiocyanate to obtain a fluorescein derivative FITC-G.The effect of aggregation-induced luminescence and aggregation-induced quenching of TPE-T,FITC-G and aptamers was verified by hydrogen-bonding base pairing.HepG2 cells were used as model cells to examine Janus short fibers for detection of circulating tumor cells.Catalase catalyzed the reaction of H₂O₂to generate oxygen to promote the movement of Janus short fibers modified with fluorescent derivatives.Specific aptamers were detected after encountering target cells to replace TPE-T and FITC-G grafts on the aptamers,leading to changes of the fluorescent derivatives from aggregated to dispersed state.The fluorescence signal was changed to construct a self-propelled micromotor that responds specifically to HepG2 cells.The effects of different aspect ratios,aptamer grafting,and hydrogen peroxide concentration on the detection effect were systematically studied.The detection results showed that the detection limit of self-propelled Janus fibers was 25 cells/ml at a concentration of 3.5%H₂O₂,and the detection range was 10²-10⁶ cells/ml.