Site-specific delivery of photosensitizer and singlet oxygen in vivo

描述(由申请人提供)：存在许多需要使用高精度技术来根除位于重要解剖部位附近的肿瘤的临床例子。传统手术和医疗方法通常无法接触到或不安全的部位包括主要血管，如颈动脉、大脑的关键区域和眼睛的部分。我们将开发一种特定部位的光纤单线态氧发生器，它有可能被用作精确的光化学手术刀，在需要细胞毒控制和手术方法无法到达的区域摧毁肿瘤细胞。提出了一种基于光纤的单线态氧定向输送装置，用于光动力治疗和药物输送。目的是设计一种非均相光动力治疗装置，它利用从多孔端释放的敏化分子在中空光子带隙光纤上的光激发，O2流经其中。拟议的研究是基于我们强有力的初步数据，该数据表明，多孔Vycor玻璃作为光敏剂载体，可以集成到中空光纤中，有效地在水溶液中产生单线态氧。假说是，从光纤设备释放的敏化剂分子将定位于肿瘤部位，并在该部位产生高浓度的单线态氧来摧毁它。这个项目的创新之处在于，到目前为止，所有的光动力疗法策略都涉及到系统地给药敏化剂；因此，我们的工作将是第一个从O2流经的光纤设备的末端切割光敏剂的工作。改进的单线态氧输送和选择性有望填补临床前光动力疗法的一个新的利基。 公共卫生相关性：通过手术从复杂部位切除肿瘤存在问题，例如当肿瘤直接与重要器官相邻时。提出了一种基于光纤的设备(用于靶向输送细胞毒性单线态氧)，以潜在地应用于疾病，如脑肿瘤，在治疗中需要精细的精度。

DESCRIPTION (provided by applicant): Many clinical examples exist which require the use of a high-precision technology to eradicate tumors that are located next to vital anatomical sites. Sites that are often inaccessible or unsafe for treatment by traditional surgical and medical methods include major blood vessels such as the carotid arteries, critical areas of the brain, and portions of the eye. We will develop a site-specific fiber optic-based singlet oxygen generator, which has the potential to be used as a precise photochemical surgical knife to destroy tumor cells in areas that require cytotoxic control and are inaccessible by surgical methods. A fiber optic-based singlet oxygen generator for targeted singlet oxygen delivery is proposed for use in photodynamic therapy and drug delivery. The objective is to design a heterogeneous photodynamic therapy device that uses the optical excitation of sensitizer molecules released from porous ends on hollow photonic band-gap optical fibers through which O2 flows. The proposed research is predicated upon our strong preliminary data showing that porous Vycor glass serves as a photosensitizer support and can be integrated to a hollow fiber optic that is effective in generating singlet oxygen in aqueous solution. The hypothesis is that sensitizer molecules released from the fiber optic device will be localized at a tumor site and that high concentrations of singlet oxygen will be produced for its destruction at that site. This project is innovative in that, to date, all photodynamic therapy strategies have involved the systemic administration of a sensitizer; our work would therefore be the first to cleave a photosensitizer from the end of a fiber optic device through which O2 flows. The improved singlet oxygen delivery and selectivity is expected to fill a new niche in preclinical photodynamic therapy. PUBLIC HEALTH RELEVANCE: Problems exist in surgically removing tumors from complex sites, such as when tumors are directly adjacent to vital organs. A fiber optic-based device is proposed (for targeted delivery of cytotoxic singlet oxygen) for the potential application in diseases, such as brain tumors where exquisite precision is needed in the treatment.