Construction Of A Multifunctional Anti-tumor System For The Delivery Of Docetaxel And Antisense Nucleic Acid Based On Graphene Oxide

Cancer is one of the major causes of death globally.Chemotherapy remains one of the most common treatment methods for cancer.Conventional drug delivery systems have several limitations.Such as docetaxel has poor water solubility.Clinical docetaxel preparations use Tween 80 as a solvent,which is prone to serious systemic side effects.Therefore,it is necessary to design a drug delivery system to deliver docetaxel to reduce toxic side effects.Graphene oxide has high specific surface area and high drug loading capacity.However,the graphene oxide has poor dispersibility in physiological solutions,and its stability can be improved by covalent modification.Functionalized graphene oxide is widely used in the field of drug loading.The application of miRNAs has become a very hot research field in human cancer treatment,representing one of the latest areas of cancer treatment.miRNA21 is one of the most studied miRNAs in tumors.miRNA21 is a tumor suppressor,which is highly expressed in a various cancers.The experimental show that down-regulating the expression of miRNA21 can inhibit the growth of tumor cells.However,the negatively charged nucleic acid cannot pass through the negatively charged cell membrane,Therefore it is necessary to design a drug delivery system to deliver it into the cell.This article relies on functionalized graphene oxide drug delivery system co-delivery Docetaxel and miRNA21 complementary DNA strand(anti-miRNA21)combined with photothermal therapy to cancer treatment.The main contents and conclusions are as follows:(1)Designed and constructed PEI functioned graphene oxide and characterize the successful preparation of nanomaterial GO-PEI.The particle size and morphology of GO-PEI was characterized.The experimental result show that GO-PEI was sheet structure,uniform and the average diameters was 200 nm.The dispersion and stability of nanomaterial GO-PEI was characterized,The experimental result show that GO-PEI did not aggregated and precipitated in physiological solutions within 5 days and better stability.Characterize which proves GO-PEI has great ability in drug and nucleic acids delivery.Construct a drug delivery system that co-load docetaxel and anti-miRNA21 to characterize the drug release.The results showed that the drug cumulative release rate at p H5.8 reached 64%±3.27 at 72 h,Compared with the neutral environment,the release effect of DTX in the simulated tumor microenvironment was better.The enzymatic stability of the drug loading system was verified.(2)Study on the anti-tumor activity of drug delivery system GO-PEI-DTX-anti-miRNA21.The verify the toxic effect of nanomaterial GO-PEI on MDA-MB-231 and Hela cells,compare the inhibit the growth of MDA-MB-231 and Hela cells,of drug delivery system GO-PEI-DTX and GO-PEI-DTX-anti-miRNA21.The results of in vitro cell experiments proved that nanomaterial GO-PEI has little toxicity to two cells,cell survival rates was concentration-dependent in drug delivery system,The concentration of DTX was 3.4 μg/m L.When MDA-MB-231 cells were treated with GO-PEI-DTX and GO-PEI-DTX-anti-miRNA21,the cell survival rates were 52%±1.01 and 45%±1.59,respectively.The concentration of DTX was 3.4 μg/m L.When Hela cells were treated with the drug-loading system GO-PEI-DTX and the drug-loading system GO-PEI-DTX-anti-miRNA21,the cell survival rates were 44%±0.36 and 38%±0.51,respectively.Combination therapy of drugs and nucleic acids has stronger apoptosis-inducing ability than single drug therapy.Laser confocal microscopy observed that the drug delivery system can quickly enter the cell to release the drug.The expression level of miRNA21 in cells was detected,and the results proved that the drug delivery system GO-PEI-DTX-anti-miRNA21 can downregulate the expressed miRNA21 in tumor cells and induce tumor cell apoptosis.The drug delivery system GO-PEI-DTX-anti-miRNA21 was irradiated with near-infrared light,and the photothermal effect of graphene oxide inhibited tumor growth.The survival rates of MDA-MB-231 cells and Hela cells under 808 nm laser irradiation were 17%±1.84 and 19%±0.87 respectively,the experimental results proved that the drug gene-photothermal synergistic treatment showed significant cancer cell killing ability.