Design And Study Of Bifunctional Graphene Oxide Drug Loading System Based On MiR-21 Response

The incidence of cancer is increasing year by year,posing a serious threat to human health.Although existing small-molecule anti-cancer drugs have obvious drug effects,they are not selective and are easily cytotoxic to normal cells or tissues,which limits their clinical application.In order to improve the anti-cancer efficiency and reduce the toxic and side effects on the body during treatment,researchers have designed a variety of drug delivery systems.In recent years,the drug delivery system mediated by nanomaterials has been widely concerned by researchers at home and abroad.Among them,grapheme oxide(GO)is rich in oxygen-containing functional groups,making it soluble in water and good in biocompatibility.In addition,graphene oxide has a low cost and a large specific surface area which is suitable for drug loading,so it is widely used in the field of drug loading.Based on the above reasons,this article relies on nanocarrier technology to design and construct two graphene oxide drug-delivery systems to reduce the cytotoxicity of small molecule anticancer drugs and enhance their therapeutic effects.The main contents are as follows:(1)Designed and constructed a drug delivery system(Dox-GO-cDNA21)based on the simultaneous delivery of doxorubicin(Doxorubicin,Dox)and antisense oligonucleotides with graphene oxide,combining the anticancer drug doxorubicin with nucleic acids to cancer cells to reduce the side effects of high concentrations of doxorubicin.The particle size of graphene oxide was optimized and characterized.The drug loading system was constructed and characterized.The enzymatic stability of the drug loading system was verified.The drug loading and drug release capacity of the graphene oxide drug loading system were determined.The uptake of graphene oxide drug-carrying system by tumor cells was verified,the safety of graphene oxide material was verified,and the inhibition of MDA-MB-231 cells by drug-carrying system was studied.The experimental results show that by synergistic delivery of 250 nM cDNA21,the dose of Dox can be reduced by about two times without impairing the efficacy of the drug.In addition,the research results show that even in the case of low-dose anti-cancer drugs,the delivery system still shows effective anti-cancer effects.In addition,the fluorescence observation of the confocal microscope showed that Dox-GO-cDNA21 can quickly enter MDA-MB-231 cells to release the drug.Moreover,the results of qRT-PCR further confirmed the anti-miR-21 silencing of miR-21 designed to be delivered to cancer cells by the designed system.(2)Because the first drug delivery system is not selective to normal cells and is susceptible to toxicity to normal cells,a bifunctional graphene oxide drug delivery system based on mi R-21 response was designed.The drug delivery system was encapsulated by HA-ADH complex,which increased its solubility in culture medium and recognition ability by CD44 receptor overexpressed cells.In addition,the drug delivery system only triggers the release of Dox through miR-21,which can inhibit the growth of cancer cells.Prepare and characterize a HA-ADH complex,design and prepare the drug-loading system,To verify the enzymatic stability of the drug delivery system,determine the drug release capacity of the drug delivery system,test the safety of graphene oxide materials,and study the uptake ofgraphene oxide drug delivery system by tumor cells,and test the drug delivery system against various tumor cells Inhibition research.