Preparation And Anti-hepatoma Effect Of Magnetic Poly D,L-lactide-co-glycolide Phenylarsine Oxide Nanoparticles

[Background] Primary hepatic carcinoma is one of most frequently malignant tumor in China. Although the new chemotherapeutics have been manufactured, they have not been widely applied in clinical, because the new chemotherapeutics have strong side effects,low effect and bad liver targeting. Recently, some investigations have indicated that phenylar -sine oxide can inhibit tumour cell proliferation ,the effect is better than that of As2O3, but the toxicity is lower. With the development of nanotechnology, there have been a new magnetism drug-carried system mediated by nanovector. In the magnetic field,the system can implement site-specific targeting drug administertion,which can raise drug concentration in the focus of infection, elevate therapeutic effect,and decrease side effect all over the body.[Objective] Take poly D,L- lactide-co-glycolide(PLGA) as the vector of phenylarsine oxide(PAO), research and optimize preparation technology,prepare magnetic poly D,L-lactide-co-glycolide phenylarsine oxide nanoparticles (M-PLGA-PAO-NP),investigate its anti-carcinoma effect and toxicity in vivo and in vitro,and detect the biodistribution in vivo.[Methods] M-PLGA-PAO-NP were prepared by ultrasound emulsion-evaporation process, and its characteristics were studied with transmission electron microscope(TEM), vibrating sample magnetometer (VSM) and high performance liquid chromatography (HPLC),and its biological distribution was evaluated by measuring iron dyeing and silver salt methods, the inhibition of tumor cell was studied by the microscope observation and MTT method, and cell apoptosis was observed by FCM; using experimental H22 Hepatoma-Bearing mice, we research therapeutic efficacy of the nanoparticles to tumor by survival time and the tumor inhibition rates; observe side effects with correlated biochemical indicator.[Result] The mean diameter of the nanoparticles was 290nm, the drug loading was 3.2%, and the encapsulation ratio was 34.2 %. The magnetic nanoparticles could effectively inhibit the growth of hepatoma cells (SMMC-7721), which depended on the effect time and concentration of drug; we established experimental H22 Hepatoma-Bearing mice;the tumor inhibition rates of PAO ,nanoparticles with 1ow dosage of PAO, and nanoparticles with high dosage of PAO on experimental H22 Hepatoma-Bearing mice were 37.34%,39.00%,and 58.09% respectively. The average tumor weight of targeted nanoparticles group was much lower than that of the same dosage of non-targeted PAO group.There was no changes in liver function, renal function and the number of leukocyte in all groups.Meanwhile, comparing with PAO group, nanoparticles with high dosage of PAO could more obviously prolong survival time of mice.[Conclusion] The nanoparticles are targeting ,delayed releasing, and stabily. In the field of magnetic, the nanoparticles have satisfactory magnetic responsibility in vivo and in vitro, could obviously elevate drug concentration in targeting intraorganic, prolong survival time of mice, reinforce the tumor inhibition rates of PAO, and relieve or avoid side effect.