Construction And Performance Study Of Drug Delivery System Based On Fluorescent Carbon Quantum Dots

Cancer is a very critical disease threatening human health,and its incidence and mortality increase annually.Chemotherapy is one of the most important methods for the treatment of malignant tumors,and doxorubicin(DOX)is the most commonly used broad-spectrum chemotherapy drug in clinic.However,the inhibitory action of DOX injection on cancer cells is lack of specificity in clinical application,and its metabolism speed is fast in vivo,which would produce serious side effects and decrease the efficacy of the drug.In addition,the excellent drug delivery system should have observability and traceability,while the traditional drug delivery system has defect in this aspect.Therefore,it is crucial to build targeted,slow controlled release and traceable drug delivery system for improving the clinical chemotherapy effect of cancer.In this thesis,the drug delivery and tracing system carrying DOX was constructed based on fluorescent carbon quantum dots(CDs),and the system was optimized.Selecting gastric cancer(MGC-803)cells as model,the response mode,drug release rule in vitro,cytotoxicity and fluorescence tracing ability of the drug delivery system were studied.The specific research contents are as follows:(1)The CDs-DOX drug delivery system was constructed and optimized.Using citric acid and urea as precursors(mass ratio 1:2),green fluorescent CDs was prepared by rapid microwave method.The CDs had a particle size of about2.6 nm,good dispersion,quantum yield of 16.7%,excellent pH stability and rich carboxyl group on the surface.The CDs-DOX drug delivery system was constructed by electrostatic adsorption,and the drug loading efficiency of the system was optimized.When the mass ratio of CDs and DOX was 1,the drug loading efficiency was up to 75.3 wt%.(2)The pH-responsive drug release property of the CDs-DOX drug delivery system was studied in detail.In vitro release profile indicated that the drug delivery system had a sensitive pH responsiveness,and the cumulative drug release ratio at pH=5.0 was about four times that of pH=7.4.MTT results showed that CDs had almost no cytotoxicity,and the inhibition ratio of the CDs-DOX drug delivery system on MGC-803 cells was almost three times that of GES-1 cells.The drug delivery system could effectively enter cells,and the cell status and drug release could be traced by fluorescence within 48 hours.Based on the above research,the system was further coated with bovine serum albumin(BSA)to construct the CDs-DOX@BSA drug delivery system,which improved the pH response sensitivity of the system and prolonged the release and cycle time of the drug in vitro.(3)A FA-targeted and pH-responsive PEI-CDs/FA-DOX drug delivery system was constructed by electrostatic self-assembly and covalent binding.The cumulative drug release ratio of the system at pH=5.0(with FR)was about fivetimes that of 7.4(without FR),and the inhibition ratio on MGC-803 cells was almost five times that of GES-1 cells.Compared with the corresponding CDs-DOX drug delivery system,the drug release process in vitro was prolonged by about 23 hours,and the cumulative drug release ratio increased by 12% at pH=5.0(with FR).