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Preparation And Study Of Antitumor Drug Sustained Release Carrier With Targeting And Marking Function

Posted on:2019-02-08Degree:MasterType:Thesis
Country:ChinaCandidate:J H ChenFull Text:PDF
GTID:2371330566986176Subject:Biomedical engineering
Abstract/Summary:PDF Full Text Request
Cancer is a major disease that threatens human health.The morbidity and mortality are high,and the total death toll is rising year by year.It has become the biggest killer of human health.Current traditional methods for treating cancer include surgery,radiotherapy,and chemotherapy,but these methods are inadequate.In recent years,targeted drug delivery systems have attracted widespread attention from many scientists.Therefore,it is of great significance to develop a targeted drug carrier capable of accurately killing cancer cells while reducing side effects.This paper focuses on the application of bioactive glass in the field of targeted anti-tumor drug sustained-release carriers and fluorescence imaging.The content is divided into two parts: the preparation and performance study of folic acid-targeting anti-tumor drug sustained-release carriers;Preparation of Er-doped bioactive glass and its research.The specific research content and conclusions are as follows:First,monodisperse micro/nano-bioactive glass microspheres were successfully prepared by sol-gel method combined with organic template self-assembly technology,and then surface modification was performed with a silane coupling agent,followed by amidation reaction coupled with anti-tumor drug methotrexate and the targeting molecule folic acid,so the targeted antitumor drug carrier MTX-BG-FA has been successfully prepared.The physical and chemical properties of the material were characterized by a series of test methods,including morphology,size,crystal form,Zeta potential,etc.The results showed that both the amination and folate coupling did not change the crystal shape and morphology of the bioglass.They were still monodisperse amorphous nanoparticles.The calculation of the folic acid graft rate was 57.5%.In vitro drug release results showed that MTX-BG-FA had a good sustained release effect and sustained release for 5 days without burst release effect.Then,cytological experiments investigated the cytotoxicity of the material,the selectivity of the material to the cell and the effect of the material on the migration behavior of the tumor cell.The results showed that BG and BG-FA were not cytotoxic,but BG-FA could even promote cell proliferation.But MTX-BG-FA exhibited significant cytotoxicity and could continuously kill cancer cells.The promotion effect of BG-FA on cell proliferation increased with the increase of the material concentration,but the cytotoxicity of MTX-BG-FA was not increasing with the increase of the material concentration.The effect of MTX-BG-FA on killing tumor cells increased as the concentration of the material increased.Afterwards,the cytotoxicity of MTX-BG-FA decreased,when the concentration was 50 ?g/ml,the cytotoxicity became greatest.The results of endocytosis showed that the affinity of BG-FA to cells was higher than that of BG,which indirectly proved that the material had target selectivity.Tumor cell migration experiments showed that BG-FA promoted cell migration,while MTX-BG-FA could inhibit tumor cell migration.Finally,Er-doped bioactive glass with different contents of erbium was successfully prepared by sol-gel method combined with template method.The test results showed that the doping of rare earth element Er3+ did not change the crystal form of the material,but slightly changed the morphology of the bioglass.Luminescence performance tests showed that BG-Er1,3,5 not only had good up-conversion luminescence properties,but also emited green fluorescence with wavelengths of 524 nm and 546 nm at excitation of 378 nm,and the intensity of emitted light increased with the Er3+ content increased.Cytological experiments showed that BG-Er1,3,5 had no cytotoxicity at low concentrations and could even promote cell proliferation at high concentrations.When the amount of erbium oxide was 3%,the material had the most significant effect on the growth of cells.
Keywords/Search Tags:folic acid, methotrexate, bioactive glass, upconversion luminescence
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