Preparation And Properties Of Graphene Quantum Dot Conjugated PEG Block Copolymer Drug Carrier Materials

Polyethylene glycol(PEG)is a widely used hydrophilic drug carrier.It is also used as a modification of drug carriers to increase its hydrophilicity and the circulation time in the blood to prevent internalization by phagocytosis to increase the effectiveness of drug delivery systems.However,the drug loading capacity of PEG as a drug carrier is not good,because simple linear PEG can only load one or two drug molecules through the two ends of the molecular chain,which greatly limits its application.Disulfide bonds are stable under normal biological conditions,but they are rapidly hydrolyzed by the high concentration of glutathione(GSH)in tumor cells and are not easily broken extracellularly.Therefore,drugs linked via disulfide bonds can be released at the tumor site and reduce damage to normal cell and tissues.Nanoparticle drug-loading systems with fluorescent properties can be prepared by conjugating graphene quantum dots(GQDs)to drug carriers.The distribution of drug-loading systems in cells and cell uptake can be monitored through the fluorescence characteristics of GQDs.And through the π-π and hydrophobic interactions load the anticancer drug paclitaxel(PTX)onto GQDs.In this context,PEG was modified by the tripeptide Glu-Lys-Glu,and the carboxyl group of the amino acid was used to increase the drug loading,and the GQDs/PEG-b-(Glu-LysGlu)/PTX nano drug delivery system was prepared by conjugate graphene quantum dot on polyethylene glycol multiblock copolymer.This drug-loading system can be biodegraded and can greatly increase the loading of anti-cancer drugs.Disulfide bonds can be used to achieve specific release in tumor.GQDs are used to monitor cancer cell uptake of the drug-loading system.The main contents and conclusions are as follows:1.The tripeptide Glu-Lys-Glu was prepared by dehydration condensation,using Lglutamic acid and L-lysine as raw materials.PEG-b-(Glu-Lys-Glu)block copolymer drug carrier was prepared by interfacial polycondensation using activated PEG and Glu-Lys-Glu,and its structure was characterized by infrared and nuclear magnetic resonance.The results show that both the target product and the intermediate were successfully prepared.2.PTX prodrug is prepared by linking 2’-OH of PTX with-COOH in 3,3’-dithiodipropionic acid.And the drug carrier,PEG-b-(Glu-Lys-Glu),was modified by cystamine dihydrochloride.PTX was linked to PEG-b-(Glu-Lys-Glu)using a disulfide bond to obtain a PEG-b-(Glu-Lys-Glu)/PTX drug delivery system.NMR protons were used to characterize PTX and PTX,and it was confirmed that the target products were successfully prepared.3.GQDs were prepared by pyrolyzing citric acid.The drug carrier,GQDs/PEG-b-(Glu-Lys-Glu),was prepared by link GQDs with PEG-b-(Glu-Lys-Glu)to co-load PTX.The loading capacity and efficiency of PTX on PEG-b-(Glu-Lys-Glu)/PTX and GQDs/PEG-b-(Glu-Lys-Glu)/PTX were measured by UV-visible spectrophotometer.The results show that PEG-b-(Glu-Lys-Glu)loading for PTX is 7.11%,loading efficiency is 71.05%.The drug loading capacity of GQDs/PEG-b-(Glu-Lys-Glu)for PTX is 8.97%,loading efficiency was 89.68%.The drug loading capacity and drug loading efficiency of GQDs/PEG-b-(Glu-Lys-Glu)are higher than PEG-b-(Glu-Lys-Glu).This result proves that the conjugation of GQDs slightly improves the loading of PTX.4.The simulate release test in 48 h of GQDs/PEG-b-(Glu-Lys-Glu)/PTX was performed by adding reduced GSH in PBS buffer solutions of different pH(5.0,6.5 and 7.4)to simulate the tumor tissue environment.The results showed that within 24 h,PTX can be released quickly and effectively at different pH conditions,and the released amounts were all over 50%.Between 24 h and 48 h,the release rate of PTX gradually slowed down and stabilized.But at pH=5.0,the amount of PTX released increased rapidly within 12 h,reaching 58.1%;between 12 h and 48 h,the released PTX increased only 27.41%,indicating that the drug-loading system has a good sustained-release effect on PTX;and the release amount of PTX at pH=5.0 is higher than the PTX released under the conditions of pH = 6.5 and pH = 7.4 at any time point,and reaches 85.51% at 48 h.It shows that the drug-loading system has a good controlled release effect on PTX.5.MCF-7 human breast cancer cells were used for cytotoxicity experiments.The results showed that the blank GQDs/PEG-b-(Glu-Lys-Glu)drug carrier had less than 10% cytotoxicity,minimal damage to cells and good biocompatibility at 48 h and 72 h.The cytotoxicity of GQDs/PEG-b-(Glu-Lys-Glu)/PTX drug-loaded system was 92% at 72 h,which was comparable to that of free PTX.It has been proved that GQDs/PEG-b-(GluLys-Glu)is an excellent carrier of PTX,which has the potential to load PTX for tumor therapy,can slow-release PTX and has low toxicity to normal cells.