Initial Practical Study Of Magnetic Macro-molecular Polymer Nanospheres On Tumor Targeting Chemotherapy

Preparation of Magnetic Polybutylcyanoacrylate Nanosphere Loaded with Aclacinomycin A and Its Effect on Gastric TumorAIM: To find a new magnetically targeted reagent loaded with an anti-cancer chemotherapeutic drug, study its toxicity and effects on gastric tumor growth in vivo and in vitro.METHODS: Iron oxide nanoparticles were synthesized by chemical co-precipitation. Acid was added to modify the particles. Magnetic polybutylcyanoacrylate nanospheres encapsulated with Aclacinomycin A (MPNS-ACM) or without Aclacinomycin A (MPNS) were prepared by interfacial polymerization. Particle diameter, shape and drug content were examined. Female BABL/c nude mice were implanted with MKN-45 gastric carcinoma tissues subcutaneously to establish human gastric carcinoma model. MPNS was injected intravenously through tail vein to nude mice as tumor model. 225OGs magnetic field was added near the tumor in half number of the mice. One or two hours later the mice were sacrificed. The tissues of heart, liver, spleen, lung, kidney, brain, skeleton muscle and tumor were taken to perform HE stain and iron stain. Another thirty mice were divided into 5 groups randomly with 6 mice each one: ACM group (8mg/kg), group of high dosage of MPNS-ACM (8mg/kg), group of low dosage of MPNS-ACM (1.6mg/kg), MPNS group and control group (normal saline). Magnets (2500 Gs) were implanted into the tumor masses in all of the mice one day before the therapy. Above-mentioned drugs were administered intravenously to the mice of every group on the first day and the sixth day. When the mice were sacrificed, tumor weight was measured, and the assay of colony forming unit-granulocyte and macrophage (CFU-GM) was performed on semi-solid culture. White blood cell, alanine aminotransferase and creatine in blood were examined, too. 3-[4-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was used to examine the viability of MKN-45 cells after incubation with different concentrations of ACM, MPNS and MPNS-ACM suspension respectively for 48 hours.The values of 50% inhibition concentration (ICso) of ACM, MPNS andMPNS-ACM were calculated.RESULTS: Stable iron oxide nanoparticles of single dispersion were prepared.Magnetic targeted system with or without Aclacinomycina A was prepared.Theparticles had obvious core-shell structure and the average diameter of the particleswas 210nm. The content of ACM in MPNS-ACM was 12.0%. The tumor inhibitionrate of ACM (8mg/kg), high dosage of MPNS-ACM (8mg/kg), low dosage ofMPNS-ACM (1.6mg/kg) and MPNS in nude mice loaded with tumor were 22.63%,52.55%, 30.66% and 10.22% respectively. There was a significant decrease in thenumber of CFU-GM of bone marrow in ACM group compared with control group,while no obvious change in those of the nanosphere groups was observed. The valuesof 50% inhibition concentration (IC50) of ACM, MPNS and MPNS-ACM were 0.09u g/ml, 97.78 u g/ml and 1.07 u g/ml respectively.CONCLUSION: MPNS-ACM is a magnetic targeted system which has core-shellstructure. Under magnetic field MPNS can be distributed in tumor tissue. The tumorinhibition rate of MPNS-ACM was much higher than that of ACM under magneticfield and the inhibition on marrow was alleviated significantly compared with ACMgroup.