Photothermal Sensitization of Biological Systems

生物系统的光热敏化

• 批准号: 6515037
• 负责人: MICHAEL A RODGERS
• 金额: $ 24.6万
• 依托单位: BOWLING GREEN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-15 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6515037
• 关键词: adenocarcinoma; apoptosis; breast neoplasms; laboratory mouse; melanoma; necrosis; neoplasm /cancer photoradiation therapy; nonhuman therapy evaluation; pharmacokinetics; photosensitizing agents; tetrapyrroles

In this new proposal, the investigators direct their efforts towards a cohesive study of photothermal action in biological and model systems. The investigation will explore the full breadth of photothermal action from its physicochemical aspects to the cell-level and animal-level manifestations. The primary objective is to seek mechanistic understanding of the effects and ramifications of depositing heat spikes in biological material using near-IR high-peak-power lasers and strongly absorbing photosensitizing agents. In the first Specific Aim the investigators will seek to establish a predictive understanding of how the molecular composition of the metallotetrapyrrole macrocycles influences the deactivation of their exited states. Under the second Specific Aim a study will be made of the dynamics of thermal energy migration out of the heat spike and of putative energy-wasting photochemical processes involving proximately situated reactant species. Under Specific Aim III the team will examine the mechanisms through which photothermal damage occurs at the cellular level and to define the factors which optimize the efficiency of such a photosensitization modality. Among questions to be considered are which sub-cellular sites are sensitive, how such sites can be targeted, and how the sub-cellular distribution of the photothermal sensitizers can influence the pathways (e.g. apoptosis vs. random necrosis) leading to cell death. In Specific Aim IV in vivo systems will be examined. This will entail a study of the efficiency of accumulation of sensitizer compounds in tumors and the resulting phototherapeutic activity. Important issues here are the nature of the primary and secondary cell/tissue targets, and the development of damage as a function of the distance from the irradiation site. In addition the team will investigate the propagation of thermal shock waves in biological materials.

在这个新的提议中，研究人员将他们的努力导向生物和模型系统中光热作用的连贯研究。这项研究将探索光热作用的全部广度，从其物理化学方面到细胞水平和动物水平的表现。 主要目的是寻求机制的理解，在生物材料中使用近红外高峰值功率激光和强吸收光敏剂沉积热尖峰的影响和后果。 在第一个具体的目标，研究人员将寻求建立一个预测性的理解如何的金属四吡咯大环的分子组成影响其退出状态的失活。 根据第二个具体目标，将研究热能迁移出热峰的动力学和假定的能量浪费光化学过程，包括位于反应物物种。 在具体目标III下，研究小组将研究光热损伤在细胞水平上发生的机制，并确定优化这种光敏模式效率的因素。 要考虑的问题包括哪些亚细胞位点是敏感的，这些位点如何被靶向，以及光热敏化剂的亚细胞分布如何影响导致细胞死亡的途径（例如凋亡与随机坏死）。 在Specific Aim IV中，将检查体内系统。 这将需要研究敏化剂化合物在肿瘤中积累的效率和由此产生的光疗活性。 这里的重要问题是原代和次级细胞/组织靶的性质，以及损伤的发展作为离照射部位的距离的函数。 此外，该小组还将研究热冲击波在生物材料中的传播。