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: $ 3.24万
• 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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=659248
• 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. **

我保持一个成功的多学科NSERC DG计划，旨在使新的基本发现在光科学，这将有助于设计更好的光敏剂的生物无机应用（和其他基于光的技术）。我的最后一个NSERC DG期间探讨了作为DNA光裂解剂的配位络合物，这些化合物可用作光动力疗法（PDT）的光敏剂。这种治疗癌症的策略，即光敏剂的光活化产生细胞毒性单线态氧，由于其对氧的依赖而受到损害，而氧在最具侵袭性的肿瘤中往往受到限制。 我的小组利用其多学科的专业知识，利用配位化学中的新物理原理，通过某些光敏剂结构引起非氧依赖性DNA光损伤。我们是第一个证明高反应性三重配体内（3 IL）激发态损伤DNA并杀死癌细胞的人，而不管氧张力如何，并且具有最好穿透组织的光波长（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。本提案将探讨3 IL配置的影响，激发态动力学在各种金属络合物类：协调，有机金属，和光喷射系统。通过对这些课程的光物理学和光化学的详细研究，我的小组将概述这些光敏剂用于光生物学应用（如PDT）的范围和局限性。我们将采用的方法包括配位络合物的合成/表征，在存在和不存在生物大分子（例如，DNA）和使用细胞的光生物学研究。学员将在化学，物理学和生物学的接口工作，掌握多学科科学所需的各种实验技术和仪器。通过该计划获得的基本见解将为生物无机应用带来更好的光敏剂，但也将使其他领域的研究人员受益，这些领域寻求具有高度光敏化激发态的热稳定金属络合物：例如发光氧传感，荧光和太阳能转换。* 我目前的NSERC DG的成功结果利用了额外的资金，并吸引了一个行业合作伙伴，该合作伙伴正在将我的一系列用于膀胱癌PDT的化合物商业化。这种伙伴关系表明了所要求的NSERC DG资金的预期成果，这将导致对光科学产生深远影响的新的基本见解。与PDT和染料敏化太阳能电池有关的技术的改进有可能通过健康和能源方面的进步使所有加拿大人受益。**