|講師：||Dr. Gerard Marriott (Department of Bioengineering, University of California-Berkeley, Professor)牧 昌次郎 助教 （電気通信大学 基盤理工学専攻）|
|題目：||[Dr. Gerard Marriott] Engineering platelets and optical probes for applications in translational medicine[牧 昌次郎] Chemistry of firefly bioluminescence|
|概要||[Dr. Gerard Marriott: Abstract] I will introduce recent work from my laboratory in two emerging areas of bioengineering. In the first part of my talk, I will discuss our approach to repurposing human platelets as living vehicles for in vivo imaging and targeted delivery of cytotoxins and immuno-therapeutics to cancer cells. In particular, I will elaborate on the chemistry detailed in Dai et al. to repurpose human platelets as tumour-targeted vehicles that involve mild surface modification of platelet membrane proteins using Traut’s reagent, and the subsequent coupling of platelets to maleimide conjugates of antibodies and other tumour targeting proteins directed against tumour biomarkers. Engineered platelets and nanoplatelets bind to tumours in the brains of mouse models of human cancer. I will also show how tumour-targeted platelets loaded with NIR-fluorophores, nanoparticles and MRI contrast agents can generate high contrast images of early-stage tumours in the brains of living mice. In the second part of my talk, I will introduce new classes of optical switch probes and optoresponsive biomaterials that have applications in high-contrast imaging and optical control of target proteins in the microenvironments of tumour cells.
[Dr. Shojiro Maki: Abstract] Firefly bioluminescence is produced by chemical reactions (luciferin-luciferase reaction) in the bodies of insects. Firefly bioluminescence finds many applications including in research in the life sciences, reporter assays, bioluminescence in vivo imaging. Research on oncology and regenerative medicine requires NIR (near infrared ray) probes. Although Amino luciferin (ca. 610 nm) and Tripluc® (ca. 630 nm) are commercially available, they do not cover the optical window region of 650-1000 nm: NIR. In an innovative approach, we synthesized AkaLumine® and TokeOni® having lmax675nm by analyzing data on structure and activity relationships. Whereas AkaLumine is the only commercially available luminescence probe with an optical window region, it has low water solubility (0.2 mg/ml). So the AkaLumine requires improvement. To resolve the problem of water solubility we succeeded in synthesizing next generation in vivo bioluminescence probe “TokeOni” with improved water solubility of 100 to 200 folds compared with AkaLumine. Furthermore, we observed a 10 fold higher luminescence than the AkaLumine during vivo imaging on mice. Although “TokeOni” is an excellent material, it has strong acidity (pH = 2), that causes problems in some animal experiment research. So we synthesized a new material “SeMpai” that has NIR activity under neutral buffer conditions. “SeMpai” will put on the international market soon.
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