Site-specific delivery of photosensitizer and singlet oxygen in vivo

描述（由申请人提供）：存在许多临床实例，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。通过传统手术和医疗方法治疗通常无法接近或不安全的部位包括主要血管，例如颈动脉、大脑的关键区域和眼睛的部分。我们将开发一种基于光纤的位点特异性单态氧发生器，该发生器有可能用作精确的光化学手术刀，以破坏需要细胞毒性控制且无法通过手术方法获得的区域中的肿瘤细胞。 提出了一种用于靶向单重态氧递送的基于光纤的单重态氧发生器，用于光动力治疗和药物递送。目的是设计一种异质光动力治疗装置，其使用从中空光子带隙光纤上的多孔端释放的敏化剂分子的光激发，O2流过该光纤。拟议的研究是基于我们强有力的初步数据，表明多孔Vycor玻璃作为光敏剂支持，可以集成到一个中空光纤，是有效地在水溶液中产生单线态氧。假设是从光纤装置释放的敏化剂分子将定位在肿瘤部位，并且将产生高浓度的单线态氧以在该部位将其破坏。 这个项目是创新的，迄今为止，所有的光动力学治疗策略都涉及敏化剂的全身给药;因此，我们的工作将是第一个从O2流过的光纤装置的末端切割光敏剂的工作。改进的单线态氧递送和选择性有望填补临床前光动力学治疗的新利基。

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.