| Project/Area Number |
07671336
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Tokyo Medical College |
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Principal Investigator |
NAGAE Tsuneyuki Tokyo Medical College, Fellow, 医学部, 助手 (70217967)
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| Co-Investigator(Kenkyū-buntansha) |
AIZAWA Katsuo Tokyo Medical College, Professor, 医学部, 教授 (40074645)
ISHIMARU Shin Tokyo Medical College, Professor, 医学部, 教授 (50112785)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Intimal Hyperplasla / Photodynamic Therapy / Scavenger Receptor / Macrophage / 新生内膜胞厚 |
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| Research Abstract |
We have previously shown that the fluorescent probe maleylated-bovine serum albumin (mal-BSA) conjugated with Texas-Red can be selectively targeted to the injured sites of arteries/IH via a scavenger receptor mediated mechanism. Therefore we conjugate photosensitizer (Chlorin e6) to maleylated-BSA for selective localization. In vivo study, endothelial cells, smooth muscle cells and macrophages in culture were analyzed for their uptake of Cle6-mal-BSA conjugates. Macrophages were found to concentrate larger amount of the conjugates than either smooth muscle cells or endothelial cells. A rat model was used to evaluate fluorophore uptake in abdominal (balloon injured) and thoracic (control) arteries for three forms of Cle6 : (1)free Cle6, (2)BSA conjugated to Cle6 and(3)mal-BSA conjugated to Cle6. Fluorescent compounds were injected 2 weeks after surgery. Four hours following injection, injured and control aorta were retrieved and examined by fluorescence microscopy. Mal-BSA/Cle6 injected group showed high fluorescence distribution in the inner side of the neointima. Free Cle6 and BSA-Cle6 did not demonstrate such high fluorescence levels. Laser irradiations were perfomed with a argon pumped dye laser tuned to 661nm. We employed two energy density : 20 J/cm2 and 40 J/cm2. Forty-eight hours after PDT,the arteries were excised and examined histologically. Intimal hyperplastic cells were significantly damaged in the mal-BSA/Cle6 injected group (20J,67%) versus Cle6 group (20J,0-20%). We conclude that mal-BSA/Cle6 localizes higher inner side of IH and functions effectively as a photosensitizer for PDT.PDT as a treatment of IH using this delivery system shows effective in this model of arterial wall injury.
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