Receptor-Targeted Photosensitzers for PDT of Cancers

用于癌症 PDT 的受体靶向光敏剂

• 批准号: 6789200
• 负责人: HARIPRASAD GALI
• 金额: $ 12.47万
• 依托单位: LYNNTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-16 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6789200
• 关键词: cell line; chemical conjugate; cytotoxicity; drug design /synthesis /production; drug receptors; folate; human genetic material tag; neoplasm /cancer pharmacology; neoplasm /cancer photoradiation therapy; neoplastic cell; ovary neoplasms; pharmacokinetics; photosensitizing agents; polyethylene glycols; tissue /cell culture; vitamin receptor

DESCRIPTION (provided by applicant): Photodynamic Therapy (PDT) is one of the emerging modalities for the treatment of cancer. Limitations associated with the current FDA approved photosensitizer (Photofrin) for cancer treatment includes prolonged cutaneous phototoxicity, complex mixture of compounds, and relatively low absorption in therapeutic window. In addition, Photofrin/R shows no selectivity for intracavity tumors such as disseminated ovarian cancers. During this project, Lynntech develops a new receptor-targeted photosensitizer based on a rational design. In this design, a far-red absorbing photosensitizer is covalently attached to a receptor-targeting moiety via a linker. The selected targeting moiety binds receptors that are overexpressed on the cancer cells with high selectivity and affinity. As a proof of the concept, during the Phase I, Lynntech will demonstrate the feasibility of this technology by synthesizing two new photosensitizer conjugates. These conjugates will be tested for in vitro cellular uptake and phototoxicity in a human ovarian cancer cell line. The proposed project could lead to the development of a clinically useful agent for the treatment of various human cancers. This will have a significant impact on the survival of cancer patients and the technology developed during this SBIR project could potentially be used for treating several thousands of cancer patients each year.

描述（由申请人提供）：光动力疗法（PDT）是治疗癌症的新兴模式之一。与目前FDA批准的用于癌症治疗的光敏剂（Photofrin）相关的限制包括长期的皮肤光毒性、化合物的复杂混合物和治疗窗内相对低的吸收。此外，Photofrin/R对腔内肿瘤如播散性卵巢癌没有选择性。在该项目中，Lynntech基于合理的设计开发了一种新的受体靶向光敏剂。在该设计中，远红吸收光敏剂通过连接体与受体靶向部分共价连接。所选择的靶向部分以高选择性和亲和力结合在癌细胞上过表达的受体。作为概念的证明，在第一阶段，Lynntech将通过合成两种新的光敏剂缀合物来证明这项技术的可行性。将在人卵巢癌细胞系中测试这些缀合物的体外细胞摄取和光毒性。拟议的项目可能导致开发一种临床上有用的药物，用于治疗各种人类癌症。这将对癌症患者的生存产生重大影响，SBIR项目期间开发的技术可能每年用于治疗数千名癌症患者。