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Study On Biological Activity Of Polyoxometalate Medicine And Polyoxometalate Nanoparticle

Posted on:2006-05-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:P P FuFull Text:PDF
GTID:1104360182998211Subject:Inorganic Chemistry
Abstract/Summary:PDF Full Text Request
Layered vanadium oxides [NH3(CH2)2NH(CH2)2NH3][V6O14] (known as LPVO) andpolyoxovandate cluster [NH3(CH2)2NH2(CH2)2NH3]4[VⅤ6VⅣ12O42(PO4)]·(PO4) 2H2O (usedname PVPO) have been synthesized and characterized by elemental analysis, IR spectra,single crystal. X-ray diffraction, in which consist of two-dimensional wavelike V-O layerparallel bc plane. Furthermore, the anti-tumor activities of two compounds were examined invitro and in vivo.(1)The study of anti-tumor activities of LPVO on three types of human cancer cells: highanti-tumor activities of LPVO on A375 was 100%(at low concentration 10-5mol/L), and alsoon MCF-7, SPC-A-1, has shown an exceeded anti-tumor-activity ability of killing 90% ofcancer cells at an low concentration of 10-4mol/L;and it was also less toxic to a humanmonocyte cell than that of 5-Fu. The 50% toxicity concentration (LD50) was higherthan2041.74 mg/kg. It was also shown that LPVO inhibited the growth and proliferation ofhuman cancer cell (Hep-A-22) in vivo;the anti-tumor activity was 51.70% more efficient than5-Fu. Immunological experiments of LPVO in vivo include observing ConA-inducedmitogenic responses of spleen cells,NK cytotoxic percentage of mice bearing Hep-A-22model and apoptosis study in vitro. These immunity and mechanisms of anti-tumor activityfrom LPVO clearly indicate that LPVO enhances the immune function of the host, and induceapoptosis to tumor cells.(2) The study of anti-tumor activities of PVPO on human cancer cells in vitro: highanti-tumor activities of PVPO on Hela and PC-3m were more than 90 %(at low concentration25μg /L ),and also the anti-tumor activity on H7402 ,MCG-803,S180 has shown 70.14%,61.90% and 98.59%, it was also less toxic to mice L929, FL, and enhancing the growth of FL,L929 cell. The 50% toxicity concentration (LD50) was higher than 2735.27%mg/kg. It wasshown also that PVPO anti-tumor on MGC-803 in vivo, anti-tumor activity was 82.4% morethan CYT. Immunological experiments of PVPO in vivo include observing ConA-inducedmitogenic responses of spleen cells,NK cytotoxic percentage of mice bearing MGC-803model and apoptosis study in vitro. These immunity and mechanisms of anti-tumor activityfrom PVPO indicate that PVPO enhances the immune function of the host, and induceapoptosis to tumor cells.(3) POMs nanoparticles were prepared and characterized .These uniform nanoparticlesused in our experiment have an average size of about 50-70 nm. In the control experiments,the micro-particles have average size of about 150 nm. Furthermore, the anti-tumor activitiesof the complexes were assayed. The results showed that after being nanoparticles, anti-tumoractivity of polyoxometalates was enhanced.(4) We have transected a human MUC18-non-expressing human prostate cancer cell linein mammalian expression vectors and obtained animal model. The knowledge learned fromfuture mechanistic, biology activity of polyoxometalates medicine and polyoxometalatesnanoparticles,it studies may allow us to understand further this unique metastasis pathway aswell as to design therapeutic means to arrest the metastasis of human cancer cells.LPVO and PVPO have been applied nation inventing patents as anti-A375,anti-PC-3m and anti-Hela drugs, which have sovereignty of knowledge in our country.These drugs have the characteristic of lower toxicity, higher activity,easily acquireraw materials and cheap Price. It shows great potential explore and develop.
Keywords/Search Tags:polyoxometalates( POMs), tumor, anti-tumor activity, nanaparticle, apoptosis
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