Folic Acid And Phosphorylcholine Oligomer Functionalized Graphene Oxide Used As Drug Carrier

Malignant tumor,the so-called cancer,has become a big problem that greatly threaten human’s health.The current means of tumor treatment mainly include operative treatment,radiation therapy,and chemotherapy.Among these methods,chemotherapy became the primary approach due to its high applicability.However,normal chemotherapy drugs have low specificities and high toxic side effects.With the development of medical technology,people found that appropriate drug delivery systems(DDSs)could help to improve the effectiveness of chemotherapy and reduce the side effects.With the development of nanotechnology over the past twenty years,a lot of new nanomaterials have been invented that lead to the rapid development of DDSs.Now,it is universally acknowledged that excellent drug carriers should have such properties as good biocompatibility,efficient loading,target delivery and controlled release,etcIn recent years,the presence of graphene has promoted the development of several scientific fields.As an important ramification of graphene,graphene oxide(GO)was regarded as a potential drug delivery due to its high specific surface area,high stability and surface paintability.In this work,we focus on synthesis of graphene oxide-based drug carrier and characterization of its morphology,delivery performance and biological properties.Detail results are demonstrated as follows:(1)Firstly,we synthesized graphene oxide by modified-Hummers method.Then GO-PCn-FA was prepared via surface modification of 2-methacryloyloxy ethyl phosphorylcholine(MPC)and 2-aminoethyl methacrylate(AMA)onto GO as a random copolymerized oligomer by a process of atom transfer radical polymerization(ATRP),and the conjugation of folic acid as targeting ligand via EDC/NHS chemistry.After that,GO-PCn-FA was characterized by X-ray diffraction,Raman spectroscopy,Fourier transform infrared spectroscopy,Nuclear magnetic resonance spectra,X-ray photoelectron spectroscopy,Transmission electron microscope,atomic force microscope,etc.Then,we studied the in vitro cytotoxicity of GO and GO-PCn-FA by cultured with three cell lines(L929,HNEPC and HepG2).The result shows that GO-PCn-FA presented a better biocompatibility.(2)We researched the delivery performance of GO-PCn-FA by selecting doxorubicin(DOX)as a model drug.Results showed that the ultimate DOX loading content is 0.21mg/mg,and a rapid release of DOX from DOX@GO-PCn-FA appeared in an acidic environment(pH=5.5).Via a series of cytotoxicity tests and a flow cytometry analysis,we found that DOX@ GO-PCn-FA shows a close cytotoxicity to cancer cells compared with the free DOX,while caused less damage to normal cells.Then A549 cells and KB cells were cultured with different concentrations of DOX@GO-PCn and DOX@GO-PCn-FA for 24h.The results showed that DOX@GO-PCn-FA caused a higher toxicity to KB cells(which has a mass of folate receptor on the surface of cytomembrane),demonstrating that the coupling of folic acid(FA)provided DOX@GO-PCn-FA a formidable and enhanced eradication effect over DOX@GO-PCn against KB tumor cells with folate receptor expression.