Nano-particles which Contained Drug Induction into Tumor Cell by Electrochemotherapy and Sonoporation

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1. Manufacture of nano-particles which contained an anti cancer drugWe made polypeptide [ (GVGVP) 25] besides the polypeptide Poly [ (GVGVP GVGVP GKGVP GVGVP GVGVP GVGVP)_<22>(GVGVP)] which made in last year and impregnated red dyes (Brebrich Scarlet Red) in the [ (GVGVP) 25] particle. Pigments were gradually discharged from them more than two weeks. We let 3. 5mg methotrexate fuse for the 30mg peptide. As a result, MTX was released more than minimum 3 days.2 Nano-particles conjugated anticancer drug and anticancer drug induction into tumor cell by sonoporation and enhanced antitumor effectsWe examined whether enhancement of the antitumor effect of sonoporation was feasible by using nano-particle of methotrexate component in mice Lewis lung carcinoma. The tumor bearing mice were divided into five groups : (1) no treatment (2) methotrexate treatment alone (3) nano-particle of methotrexate component treatment alone (4) methotrexate treatment followed by sonoporation(5)nano-particle of methotrexate component treatment followed by sonoporation. Sonoporation was applied to the tumors after intraperitoneal injection of drugs. Tumors of the mice were measured every 2 days after treatment. Differences in the rate of tumor volume increase between No. (4), (5) groups and other three groups were significant. As for No. (5) group in particularly, antitumor effect was enhanced. The methotrexate content of the tumor tissues from the sonoporation groups (No. (4), (5)) were higher than other groups. To confirm the promotion of methotrexate induction in vivo tumor cells by sonoporation, fluorescence conjugated MTX was administered into tumor cell. In the presence of sonoporation, fluorescence-positive cells were observed, while only a weakly positive area was observed in the absence of sonoporation.