Study On Folic Acid Click Chemistry Functionalized Gold Materials And Its Sensing Properties

The term"click chemistry"was first introduced by Sharpless and co-workers in 2001, which describes a modular approach to organic synthesis. The reaction is characterized by its high chemoselectivity, modularity, near-perfect yield and biocompatibility. Fe₃O₄@Au core-shell nanoparticles, maintaining both the advantages of chemical stability and biocompatibility of Au and the magnetic nanoparticles of Fe₃O₄, can effectively overcome the shortcomings of magnetic nanoparticles, such as poor stability, easy aggregation and low surface functional group. Folic acid (FA) and FA-derivatives are stable, inexpensive, nonimmunogenic and applicable over a wide range of tumors. FA and FA-derivatives have a high affinity for folate receptors (FRs) on the cancer cell surface and can be internalized via endocytosis, which provides basis for targeting theropy of cancer cells in medical field. This paper describes the alkyne-functionalized FA was modified to as-prepared Fe₃O₄@Au core-shell nanoparticles using click chemistry for identifying leukemia cell K562. In addition, the alkyne-functionalized FA was modified to gold electrode using click chemistry and was studied in electrochemical method. FA modified to gold electrode was also used to sense leukemia cell K562. The main research contents are as follows:The synthesis and characterization of gold-coated Fe₃O₄ nanoparticles (Fe₃O₄@Au) core-shell nanoparticles was describe. Fe₃O₄ magnetic nanoparticles were prepared by co-precipitation method and then used as seeds for the reduction of gold precursors to produce Fe₃O₄@Au. The as-synthesized nanoparticles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), energy dispersive spectrometer (EDS), powder X-ray diffraction (p-XRD), Fourier-transform infrared (FTIR) spectrum and vibrating sample magnetometer (VSM). The Fe₃O₄@Au nanoparticles have a particle size 20 nm and can be separated quickly from solution by an external magnet.The Fe₃O₄@Au nanoparticles were modified by 1-azidoundecane-11-thiol and 6-mercapto-1-hexanol. In the presence of Cu(I) catalysts, the alkyne-functionalized FA was grafted on the Fe₃O₄@Au nanoparticles via a reliable, selective, robust click reaction. After the reaction, the nanoparticles were incubated with leukemia cell K562 and we observed the cells by means of optical microscopy by an external magnet. The results showed that cells moved towards the side of the external magnetic field by an external magnet after incubation with nanoparticles. This indicated that the nanoparticles modified with alkyne-functionalized FA had been well combined with the folate receptors (FRs) on the cancer cell surface, which showed a good identification of cancer cells.The strategy of click chemistry was also applied to modify macroscopic gold electrode. Structurally well-defined azide-terminated organic self-assembled monolayers (SAMs) were formed on gold electrode surface from a available mixture solution of 1-azidoundecane-11 -thiol and 6-mercapto-1-hexanol. Subsequent, in the presence of Cu(I) catalysts, the alkyne-functionalized FA was grafted on gold electrode surface by click chemistry. And then the FA modified electrode was incubated with leukemia cell K562 at 37℃and was monitored by electrochemical method and optical microscopy. The redox peak at the potential of 0.60 V showed that the FA had been fixed to the electrode. With the incubation time increasing (20 min, 40 min, 60 min) in PBS (pH=7.4), the corresponding electrochemical impendance spectroscopy resistance increased ceaselessly, and the amount of cells attached to the gold electrode surface increased. The results demonstrated that alkyne-functionalized FA had been modified to the gold electrode, and alkyne-functionalized FA had been well combined with the FRs on the cancer cell surface, which showed a good identification of cancer cells.