报告题目：Real-Time Near Infrared Fluorescence Imaging: research tools with the potential for clinical use 报 告 人：Prof. Donal O’Shea (Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 爱尔兰皇家外科医学院) 时 间：2016年3月22号（星期二）上午 10:30分 地 点：仙林化学楼 H201报告厅 邀 请 人：强琚莉 副教授，王乐勇 教授 Group website: www.rcsi.ie Abstract Fluorescence imaging, utilizing molecular fluorophores, often acts as a central tool for research into fundamental biological processes. It also offers huge future potential for human imaging coupled to therapeutic procedures such as fluorescence guided surgery. We have recently developed a new class of near infrared (NIR) fluorophore from which excellent in vitro and in vivo imaging probes can be developed.1a-d But in spite of the advantages offered by longer wavelength NIR emissions a common limitation with live cell fluorescence imaging is the difficulty in discriminating non-specific fluorescence from fluorescence localized at a specific region of interest. This can restrict imaging to individual time points at which non-specific background fluorescence has been minimized. It would be of significant advantage if the fluorescence output could be modulated from off to on in response to specific biological events of interest as this would permit imaging of such events in real time without background interference. In this presentation, the design, synthesis, in vitro and in vivo evaluation of a bio-conjugatable NIR-fluorochromes 1 which uses lysosomal pH as the NIR-fluorescence switching trigger will be described (Figure, structures 1a,b).2 NIR-fluorophore 1a permits continuous real-time 4-D imaging of cellular uptake, trafficking and efflux processes as fluorescence signal solely arises from the lysosomes. This is clearly shown by lysosomal red/green co-emission with LAMP1-GFP transfected HeLa cells (Figure).2 Application of this 4-D imaging technique to real-time capture of the cellular responses to Prodigiosin 2, a bacterial natural product reported as a lysosomal de-acidifying agent will also be illustrated (Figure, structure 2). Results from the use of this off/on pH NIR-fluorescence switching for in vivo tumor imaging using the cyclic- RGD peptide conjugated fluorophore 1b will also be described. References: [1a] Wu Dan, O'Shea D.F. Org. Lett. 2013, 15, 3392. [1b] Palma, A.; Alvarez, L.A.; Frimannsson, D.O.; Grossi, M.; Quinn, S.J.; O’Shea, D.F. J. Am. Chem. Soc. 2011, 133, 19618. [1c] http://www.youtube.com/watch?v=FjipbGTf8w4. [1d]Wu Dan, O'Shea D.F. Chem. Commun. 2015,51, 16667. [2] Grossi, M. O’Shea D.F. et al Nat. Commun. 2016, in press, DOI: 10.1038/ncomms10855. Biography Prof. Donal O’Shea received his PhD degree in Chemistry from University College Galway, Ireland in 1994. He held post-doctoral positions in the University of Edinburgh (Scotland) and Carnegie Mellon University, Pittsburgh (USA) following which he was a research scientist at Eastman Kodak Company in Rochester, New York. In 1999 he returned to academia to a position in University College Dublin and was promoted to Professor of Chemistry in 2007. In 2013 he moved to the Royal College of Surgeons in Ireland where he is the current Prof. and Head of the Department of Pharmaceutical and Medicinal Chemistry. He has received the Royal Society of Chemistry, Inaugural 2012 North/South of Ireland lectureship award, is a member of the Editorial Board of Chinese Chemical Letters and the co-organizer of the Bilateral China-Ireland Symposia on Frontiers in Synthetic Chemistry. He has held visiting professorship positions at Donghua University Shanghai, University of Rennes, and the École Nationale Supérieure de Cachan Paris. His research interests include near-infrared fluorescent imaging, medicinal chemistry and synthetic organometallic chemistry. |