| Project/Area Number |
20015045
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Sojo University |
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Principal Investigator |
MAEDA Hiroshi Sojo University, 薬学部, 教授 (90004613)
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| Co-Investigator(Kenkyū-buntansha) |
FAN Jun 崇城大学, 薬学部, 講師 (20412736)
NAKAMURA Hideaki 崇城大学, 薬学部, 助手 (30435151)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥9,500,000 (Direct Cost: ¥9,500,000)
Fiscal Year 2009: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2008: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | HSP32阻害剤 / HO-1阻害剤 / 高分子型制癌剤 / DDS / 腫瘍ターゲッティング / Znプロトポルフィリン / 新しい光化学療法 / PEG化制癌剤 / 腫瘍ターゲラィング / 腫瘍ターゲティング |
|---|
| Research Abstract |
We prepared two types of polymeric drugs having anti-HO-1 and antitumor activities, (i) PEGylated ZnPP (covalently linked ) and (ii) SMA-ZnPP micelles. Cell uptake was several fold faster in SMA-ZnPP micelles than PEG-ZnPP conjugates. They exhibited both in vitro cytotoxicity and in vivo antitumor activity having IC_<50> of 1-7μM and 10mg/kg in vivo respectively. They also exhibited enhanced cytotoxicity to human tumor cells (CML cell line, K562 ; ATL cell line, MT-2 ; esophageal cell line, Kyse 510) in culture under the exposure to LED light at 420nm. Mouse tumors were more effectively suppressed with SMA-ZnPP plus LED light at 420nm than drug alone both in vivo and in vitro. PEG-ZnPP conjugates (covalent) undergo hydrolytic cleavage by serine and thiol proteases in the tumor tissue and released free ZnPP, whereas SMA-ZnPP micelles underwent micelle disintegration upon the contact with to cell membrane components such as lecithin, and released the drug ZnPP effectively in cells.
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