Synthesis Of Graphene-based Drug Carriers And Their Applications In Tumor Theranostic

Theranostic as an emerging therapeutic strategy has highlighted its superiority in biomedicine.Specifically,Theranostic is a combination of diagnostics and therapy,aiming at the tumor localization through imaging and simultaneously drug delivery.It is vital to develop multifunctional nanocarriers which are capable of tumor imaging,targeted drug delivery as well as controlled drug release.Therefore,we focus on the construction of graphene-based nanocarriers for tumor targeted imaging using SERS spectroscopy and controlled drug release.It is expected to provide a new platform for precise diagnosis,treatment and simultaneously real-time monitoring of the treatment process.This platform is of great significance to achieve efficient personalized therapy.The details are as follows:(1)A novel graphene-based drug carrier with dual-targeting abilities was developed to delivery mixed drugs to tumor cells.The targeting property of the drug carrier was studied under an external magnetic field.The results indicated that the drug carrier exhibited both of the magnentic and antibody targeting to SKBR3 cells.SERS-Fluorescence joint spectroscopy was used for mapping of tumor ceils,and real-time monitoring of intracellular locations of the drug and carriers.The results showed that the carriers were first located in the acidic lysosome where drug was released,then the carriers were escaped to the cytoplasm while drug was distributed in the entire cell.The cell survival experiments indicated that enhanced cytotoxicity for SKBR3 cells was achieved owing to the targeted drug delivery;the killing effect of tumor cells was further improved by the combinational therapy of mixed drugs compared to that of single drug.In addition,the effect of the adsorbed mixed drugs status on the therapeutic efficiency was studied through fluorescence spectra,thus a possible drug adsorption model was provided.(2)A disulfide bond-containing drug delivery system based on graphene was developed for the application in tumor theranostic.In this system,drug was linked through a disulfide bond.Compared with the conventional π-π loading strategy,this disulfide bond-based loading strategy was capable of higher drug loading capacity.Meanwhile,the drug release efficiency was improved under the same stimulation.The drug release was effectively triggered by intracellular glutathione.Intrinsic SERS signals from nanocarriers and drug molecules were used to tracking intracellular release dynamics in real-time which were very sensitive in this process.(3)A nuclear-targeted graphene quantum dot-based drug delivery system was constructed.Owing to the ultra small size and specific nuclear localization peptide,Graphene quantum dots can overcome the barrier of nuclear membrane and effectively deliver drug to the nucleus.The results showed that this nuclear-targeted drug delivery significantly improved the killing efficiency of tumors.In addition,graphene quantum dots served as the donors of FRET pairs,while drug served as acceptors.Nuclear imaging and simultaneously real-time tracking of drug release dynamics were achieved through the FRET signals.The results showed that the FRET signal was very sensitive to the interaction between graphene quantum dots and drug.Graphene quantum dots and drug entered into the nucleus as conjugates,and after that the drug was released.Thus,this proposed drug delivery system is ideal in the application of theranostic.