2007 Fiscal Year Final Research Report Summary
Study on diagnosis and treatment of cancer in the gastrointestine using cancer-recognizable nanocarriers
| Project/Area Number |
18590160
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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 |
Medical pharmacy
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| Research Institution | Setsunan University |
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Principal Investigator |
SAKUMA Shinji Setsunan University, Faculty of Pharmaceutical Sciences, Associate professor (80388644)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Shinji Setsunan University, Faculty of Pharmaceutical Sciences, Professor (00158156)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Colorectal cancer / Endoscopy / Imaging agent / Lectin / Nanomedicine |
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| Research Abstract |
We designed a novel colonoscopic imaging agent that can recognize tumor-derived changes in the large intestinal mucosa. The agent was composed of peanut agglutinin (PNA)-immobilized polystyrene nanospheres with surface poly(N-vinylacetamide) (PNVA) chains encapsulating fluorescent coumarin 6. PNA was a targeting moiety that binds to P-D-galactosyl-(1-3)-N-acetyl-D-galactosamine(Gal-β(1-3)Cra1NAc), which is the terminal sugar of the Thomsen-Friedenreich (TF) antigen that is specifically expressed on the mucasal side of colorectal cancer cells. PNVA was expected to enhance the specificity of PNA for the carbohydrate residues by reducing nonspecific interactions between imaging agents and normal tissues. Coumarin 6, which was expected to provide endoscopically detectable fluorescence intensity, was encapsulated into polystyrene cores of nanospheres through their strung hydrophobic interactions. Agglutination of normal and Gal-(1-3)GalNAc-expressing erythrocytes in the presence of PNA-immo
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bilized fluorescent nanospheres with surface PNVA chains (imaging agents) showed that PNA was actively immobilized on the nanosphere surface with a strong affinity for Gal-β(1-3)CralNAc, which was equivalent to that of intact PNA, and that PNVA enhanced the specificity of PNA for the carbohydrate residue as we expected. In vitro studies on interactions between imaging agents and various cultured human cells indicated that imaging agents bound to the TF antigen-expressing cancer cells with high affinity and specificity by recognizing Cral-β(1-3)Ga1NAc which is the terminal sugar of the antigen. We are just examining the usefulness of imaging agents in tumor-bearing animal models. The localization of fluorescence derived from imaging agents was observed in the large intestinal mucosa of tumor-bearing mice, but significant fluorescence in the large intestinal mucosa of normal mice was not observed. Preliminary in vivo data suggest that colorectal cancer can be detected by observing a clear fluorescent contrast between normal and cancerous tissues under a fluorescent endoscope. Details concerning in vivo studies will be described in future. Less
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