Synthesis, Characterization And Targeting Of Hepatocellular Carcinoma By Functionalized Carbon Nanotubes / Graphite Oxide

Many traditional anticancer drugs can kill the cancerous tissues, but they alsolead to adverse side-effect on normal tissues. Since the cost of developing a new drugis very high today. Designing a drug carrier modified with targeting group is one ofthe best ways to realize the drug delivery to cancerous tissues.Because of the unique properties of mechanics, optics, ectronics, heat andmagnetism, nanomaterials have been widely used in biomedieal fields. As two typicalmaterials of nanomaterials, carbon nanotube (CNTs) and graphene oxide (GO) canload anticancer drugs and transport to the tumor cells. Doxorubicin hydrochloride(DOX), an anticancer drug,can be loaded on the carbon nanotube and graphene oxidethrough a π-π stacking interaction. In this study, we use multi-walled carbonnanotubes and graphene oxide as drug loading templets and focus on the synthesis,characterization and liver targeting applications of multifunctional carbon nanotubeand graphene oxide drug loaded complexes.（1）Multi-walled carbon nanotubes and graphene oxide were modified withpolyethylenimine (PEI) to improve the stability in water medium through the covalentbond interaction, sequentially modified with fluorescein isothiocyanate (FITC) andpoly(ethylene glycol)-linked lactose acid(PEG-LA), followed by acetylation of theremaining PEI terminal amines to synthetize the lactose acid modified carbonnanotube and graphene oxide complexes. The structure and properties of themultifunctional carbon nanotube and graphene oxide were characterized and analysedby1HNMR, UV-Vis, TEM, Zeta potential et al.The result shows that lactose acid wassuccessfully modified on the carbon nanotube and graphene oxide complexes. Thedrcrease of zeta potential indicated that the remaining amine groups of PEI wascompletely neutralized by the acetic anhydride.（2）Taking the drug loadings (dl) and encapsulation efficiency (ee) as theevaluation index. Through the change of pH value, and the mass ratio of DOX andcarbon nanotube/graphene oxide complexes, a drug loading complex with pHsensitivity, targeting and fluorescence was obtained by using the best conditions toload DOX. After the drug releaseing in different pH condition, the result shows that inacetic acid buffer solution (pH5.8, tumor cell environment), the drug release rate ofcarbon nanotube and graphene oxide complexes ware significantly higher than that in PBS buffer solution (pH7.5, close to the in vivo environment). Realize the purpose ofreducing the side-effect on normal tissues.（3）The therapeutic efficacy of the multifunctional carbon nanotube andgraphene oxide drug loading complexes ware tested using SMMC-7721cells by3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and theproperty of liver targeting was tested using SMMC-7721cells and PIEC cells. Thecell experiment shows that the therapeutic efficacy of the multifunctional carbonnanotube and graphene oxide drug loading complexes was only related to the DOX.The results of confocal microscopic imaging and flow cytometry indicate that themultifunctional carbon nanotube and graphene oxide drug loading complexes cantarget the SMMC-7721cells which overexpress asialoglycoprotein(ASGPR) receptors.Realize the target delivery of DOX to SMMC-7721cells.