Experimental Research On Preparation And Targeted Therapeutic Effect Of Epirubicin-polybutylcyanoacrylate Magnetic Nanoparticles

Objective:to prepare the epirubicin-polybutylcyanoacrylate magnetic nanoparticles (EPI-PBCA-MNPS) by emulsion polymerization method,examine its physical and chemical properties,and inspect its targeted distribution in mice. Type MG-63and U2-OS human osteosarcoma cells by tumor cells in vitro experimental study, produced in nude mice transplanted tumor model, observe the targeted therapy efficacy of EPI-PBCA-MNPS by the transplanted tumor in nude mice. Provide a new possibility for the targeted treatment of osteosarcoma.Methods:(1)we synthesis EPI-PBCA-MNPS by chemical co-precipitation and emulsion polymerization using FeCl2·4H2O、 FeCl3·6H2O、the epirubicin hydrochloride adriamycin (EPI)、a-polybutylcyanoacrylate.(2) observe its physical form by the transmission electron microscope,measure its saturation magnetization using a vibrating sample magnetometer (VSM), measure the drug envelopment rate and the quantity of drug load of EPI by ultraviolet-visible light spectrophotometer inspect its targeted distribution in mice.(3)observe the proliferation and invasion of type MG-63and U2-OS human osteosarcoma cell by CCK-8and Transwell experiment.(4) produce nude mice transplanted tumor model, inject EPI-PBCA-MNPS into the nude mice to observe the efficacy of targeted therapy in nude mice transplanted tumor.Results:Successfully prepared stable colloidal solution, its average particle size was184.6nm in transmission electron microscopy, the saturation magnetization was0.558emu/g, the drug envelopment rate was90.73%, and the quantity of drug load was10.68%. The magnetic nanoparticles enriched in the target organ, and the drug concentration was lower in the non-target organs (blood, heart, liver, lung) by the role of the external magnetic field. CCK-8experiment showed that the magnetic nanoparticles inhibit the proliferation of type MG-63and U2-OS human osteosarcoma cells, Transwell experiments showed that the drug can reduce invasion of the two type cells. Injection the magnetic nanoparticle drug into the nude mice t umor model, a certain strength of the magnetic field is applied to the tumor site, results showed an obvious inhibitory effect, inhibition rate of tumor volume was96.26%, inhibition rate of tumor weight was88.82%. The tumor biopsy showed an obvious tumor necrosis.Conclusion:The magnetic nanoparticle we prepared showed some good characteristics such as good stability, strong targeting, high drug envelopment rate and quantity of drug load and simple preparative method. The vitro experiments showed EPI-PBCA-MNPS inhibited the proliferation and invasion of type MG-63and U2-OS human osteosarcoma cell. Tumor model experiment showed that, EPI-PBCA-MNPS significantly inhibited the growth rate of nude mice transplanted osteosarcoma tumor with a strong target. The drug was expected to become a new type of osteosarcoma chemotherapy drugs, and to provide new options for osteosarcoma chemotherapy.