| Co-Investigator(Kenkyū-buntansha) |
ONO Koji Kyoto University, Research Reactor Institute, Professor, 原子炉実験所, 教授 (90122407)
OGURA Koichi Nihon University, College of Industrial Technology, Professor, 生産工学部, 教授 (60059681)
KOBAYASHI Hisao Rikkyo University, Institute for Atomic Energy, Professor, 原子力研究所, 教授 (10062605)
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| Research Abstract |
We performed the study of development of enhanced effects of BNCT with tumor specific gene therapy.
(1) We prepare a polyethylene-glycol (PEG) binding liposome entrapped ^<10>B compound for the delivery system. After thermal neutron irradiation of mice injected with ^<10>B-bare liposome or ^<10>B-PEG-liposome, AsPC-1 tumour growth was suppressed relative to controls. Colon 26 tumor was disappeared by BNCT with the injection of Transferrin-^<10>B-PEG-Liposome. Injection of Transferrin-^<10>B-PEG-Liposome and ^<10>B-PEG-liposome caused the greatest tumour suppression with thermal neutron irradiation in vivo.
(2) We performed neutron capture autoradiography(NCAR) using CR-39 plastic track detectors. The CR-39 detectors attached with samples were exposed to thermal neutrons or cold neutrons at Rikkyo University, PSI, Institute of Jozef Stefan or Sakley Institute. We can increase the accumulation of ^<10>B atoms in the tumor tissues by PEG-liposome, which increase the retension in the blood f
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low and escape the phagocytosis by RES.
(3) We developed the novel small sized palsed neutron generator. This neutron generator will be applied to BNCT.
(4) It is necessary to increase the transfectional efficiency when we use non-viral vector on cancer gene therapy. We have prepared new typed plasmid DNA-cationic lipoplexes, called quatenary complex (" Qplex "), and evaluated DNA delivery efficiency. Qplex is composed with cationic liposome, pDNA, protamine and transferrin. The lipid of liposome M-( α-trimethylammonioacetyl)-didodecyl-D-glutamatechloride (TMAG) / dilauroyl-phospatidylcholine (DLPC) / dioleoylphospatidyl-ethanolamine (DOPE) (1 : 2 : 2). The transfectional efficiency of lac Z gene is increased to 52% with Qplex from 4 % with conventional cationic lipoplexes in Xgal staining. The transfection efficiency is superior in the existence of serum.
(5) In order to increase the transfection efficiency in non-viral vector gene therapy, a novel fusogenic peptide, JTS-1, was evaluated in Lipoplex. Luciferase activity in cancer cell lines was greatest in the using JTS-1/LPD complex. The high transfection effeciency was observed by Xgal staining. The mean diameter of LPD is 50 nm and it is so compact compared to lipoplex ( about 600nm ). Fifty percent tumor growth suppression of AsPC-1 cells was shown at the 0.4μg per ml of tob, "a novel tumor suppressor ", DNA plasmid using JTS-1/LPD complex. The suppressive effect was caused to induction of apoptosis. Less
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