Investigation of Metal-Organic Hybrids as Photosensitizers for Bioinorganic Applications

金属有机杂化物作为生物无机应用光敏剂的研究

• 批准号: RGPIN-2015-04364
• 负责人: McFarland, Sherri
• 金额: $ 3.28万
• 依托单位: Acadia University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=612921
• 关键词: Investigation; Metal; Organic; Hybrids; Photosensitizers

I maintain a successful multidisciplinary NSERC DG program aimed at making new fundamental discoveries in the photosciences that will facilitate the design of better photosensitizers for bioinorganic applications (and other light-based technologies). My last NSERC DG period explored coordination complexes as DNA photocleaving agents, compounds that have utility as photosensitizers for photodynamic therapy (PDT). This strategy for treating cancer, whereby light activation of a photosensitizer produces cytotoxic singlet oxygen, is compromised by its reliance on oxygen, which is often limited in the most aggressive tumours.  My group used its multidisciplinary expertise to exploit novel photophysical principles in coordination chemistry to elicit oxygen-independent DNA photodamage by certain photosensitizer constructs. We were the first to show that highly reactive triplet intraligand (3IL) excited states damage DNA and kill cancer cells regardless of oxygen tension, and with wavelengths of light that penetrate tissue best (red and near-infrared). This fundamental insight spawned considerable interest from the academic community as well as industry. This proposal will explore the influence of 3IL configurations on the excited state dynamics in a variety of metal complex classes: coordination, organometallic, and photoejecting systems. Through a detailed investigation of the photophysics and photochemistry of these classes, my group will outline the scope and limitations of these photosensitizers for photobiological applications such as PDT. The methodologies that we will employ include synthesis/characterization of coordination complexes, photophysical/photochemical studies in cell-free environments in the presence and absence of biological macromolecules (e.g., DNA), and photobiological studies using cells. Trainees will work at the interface of chemistry, photophysics, and biology, mastering the diverse experimental techniques and instrumentation necessary for multidisciplinary science. The fundamental insight gained through this program will lead to better photosensitizers for bioinorganic applications, but will also benefit researchers in other fields that seek thermally stable metal complexes with highly photosensitizing excited states: luminescent oxygen-sensing, photocatalysis, and solar energy conversion as examples. Successful outcomes from my current NSERC DG leveraged additional funding, and attracted an industry partner that is commercializing a family of my compounds for bladder cancer PDT. This partnership demonstrates the anticipated outcome of the requested NSERC DG funding, which will lead to new fundamental insights in the photosciences with far-reaching impact. Improvements in technology related to PDT and dye-sensitized solar cells have the potential to benefit all Canadians through advances in health and energy.

我维持着一个成功的多学科NSERC DG项目，该项目旨在光科学领域取得新的基础发现，这将有助于为生物无机应用（以及其他基于光的技术）设计更好的光敏剂。我在NSERC的最后一段DG时期探索了配合物作为DNA光切割剂，这些化合物作为光动力治疗（PDT）的光敏剂。这种治疗癌症的策略，即光敏剂的光激活产生细胞毒性单线态氧，由于对氧气的依赖而受到损害，在最具侵袭性的肿瘤中，氧气通常是有限的。我的团队利用其多学科专业知识，在配位化学中利用新的光物理原理，通过某些光敏剂结构引起不依赖氧的DNA光损伤。我们首次证明了高活性的三联体配体内（3IL）激发态破坏DNA并杀死癌细胞，而不考虑氧张力，并且使用穿透组织最好的光波长（红色和近红外）。这一基本见解引起了学术界和工业界的极大兴趣。