Preparation And Characterization Of Chitosan Derivative Drug Carriers Containing?paclitaxel And Graphene Ouantum Dots

Due to various causes of cancer and malignant behaviors such as invasion and migration after the onset of cancer,cancer has become the most destructive disease.Although significant progress has been made in human medicine,the existing methods are still difficult to eradicate cancer.With the concept of targeted therapy,the use of chemically modified amphiphilic polymers to encapsulate anticancer drugs as targeting vectors for cancer cells has become a research hotspot.The application of polymer drug carrier materials can not only reduce the anti-cancer drugs to the human body.The side effects,but also can increase the chance of drug uptake by cancer cells,improve drug utilization,and because it has the effect of sustained release,can extend the drug injection cycle,reduce the patient's pain,enhance quality of life,improve the cure rate.In this thesis,a novel and efficient folate-polyethylene glycol-chitosan-palmitic acid nanomicelle?FA-PEG-CS-PA NPs?was prepared as a targeted drug carrier material for co-loaded paclitaxel and graphene quantum dots.First,the low-molecular-weight?40 kDa?chitosan was chemically modified with polyethylene glycol and folic acid,and then synthesized with palmitic acid to prepare an amphiphilic FA-PEG-CS-PA-targeting chitosan.derivative.Coencapsulated with graphene quantum dots and paclitaxel were used to prepare paclitaxel-loaded nanomicelle PTX NPs and co-loaded paclitaxel-graphene quantum dot nanomicelles GQDs PTX NPs.The structure and dimension of the polymer were tested by FT-IR,XRD and TEM.It was proved that the target product was successfully prepared.The biological activity of the prepared nanomicelles was verified by in vitro cell experiments,and the uptake of nanomicelles by cancer cells was assessed using a fluorescence inverted microscope.In vitro release experiments and entrapment rate assays were also performed.Experiment result shows:1.The obtained product was consistent with the target product by FT-IR and XRD measurements.As can be seen in the TEM electron micrographs,the prepared nanomicelles have good dimensional stability.The size of the prepared nanomicelles was investigated by a Malvern dynamic laser particle size analyzer.The size of the blank nanoparticles was 16.34 nm.The size distribution of the nanomicelles coated with paclitaxel was stable at about 33 nm-110 nm,and the quantum dots were co-coated.Paclitaxel nanomicelles are dimensionally stable between 124-253 nm.2.The paclitaxel-loaded nanomicelles prepared with different feed ratios were tested,and the encapsulation efficiency and drug loading rate were tested.The entrapment efficiency was measured during the increase of shell to drug ratio from25:1 to 5:4.From 93.4%to 79.1%,the average entrapment efficiency was 88.6%,the drug loading rate rose from 2.8%to 12.5%,and the average drug loading rate was8.2%.In a test simulating the pH release rate of human normal tissue and cancer cell tissues,paclitaxel released slowly and uniformly from the shell material at pH=7.4,and no sudden release occurred.The cumulative release rate for 47 hours was 47.1%..In an environment where the pH=5.6 mimics the tissue fluid of the tumor cells,the drug release rate is significantly accelerated,and the cumulative release rate in the 200hours is 74.4%.3.HeLa cells were cultured with different concentrations of nanomicelles to investigate the cytotoxicity of the drug-loaded nanomicelles,and the toxicity of the blank particles and free paclitaxel drug preparations on the cells was compared,and MTT experiments were performed.The prepared nanomicelles have good biological activity.The survival rate of HeLa cells in the nanomicelles coated with paclitaxel for24 hours at a concentration of 20?g/mL dropped below 20%,while the free paclitaxel group still had nearly 40%survival.cell.By calculating the Ic₅₀ values of drug-loaded micelles and free paclitaxel,the Ic₅₀ of the drug-loaded micelles was 37.2?g/mL and the Ic₅₀ of free paclitaxel was 73.7?g/mL.This shows that nanomicelles coated with drugs have a higher efficacy than traditional paclitaxel drugs.The blank nanomicelles without paclitaxel did not show any inhibitory effect on HeLa cells,and the survival rate of cancer cells rose to over 100%with increasing concentrations.MCF-7 cells and A549 lung cancer cells were cultured at same concentrations in vitro?20?g/mL?for different periods of time.MTT assay results showed that A549 lung cancer cells were coated with quantum dots and paclitaxel and paclitaxel-coated nanomicelles at 24hours.The survival rates of MCF-7 human breast cancer cells were around 50%and40%,respectively,while the free paclitaxel-cultured cells were all around 60%.It was demonstrated that the prepared micelles were all superior to traditional drugs in drug efficacy and had good targeting and stealth properties,and the micelles coated with quantum dots did not affect the biological activity of the micelles.