Self-Illuminated PDT Platform for Highly Specific Diagnosis and Therapeutics for Deep Sited Tumor

用于深部肿瘤高度特异性诊断和治疗的自发光 PDT 平台

• 批准号: EP/Y036646/1
• 负责人: Molly Stevens
• 金额: $ 23.84万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY036646%2F1
• 关键词: Self; Illuminated; PDT; Platform; Highly

Early diagnosis and treatment of cancer have attracted extensive attention, however, there is still a shortage of techniques that integrate tumor imaging and therapeutics. Photodynamic therapy (PDT) that involves functional photosensitive dyes has been considered as a potential solution. PDT mainly relies on light-activated photosensitizers (PSs) to (1) visually label cancer with luminescence and (2) generate excessive toxic reactive oxygen species (ROS). However, one of the main reasons that hinders PDT application is the limited tissue penetration of excitation light. Hence, solving the excitation problems of PSs in deep sites and overcome the tissue obstacles are of great significance for efficient all-in-one cancer diagnosis and treatment. This project will develop a Multi-Function Integrated Self-Illuminated PDT platform that can overcome the limited light penetration in conventional PDT, enabling synchronous diagnosis and treatment of orthotopic tumors. BODIPY-luminol dyads will be constructed by connecting BODIPY PSs (with long triplet lifetime) with afterglow luminol. Upon triggered by the specific tumor microenvironment (TME), the dyads can be activated by chemical energy to singlet excited state (S1), then undergointersystem crossing to triplet excited state, where the dyad sensitize O2 to yield 1O2 for PDT. The PDT process relies on the chemical reaction between luminol and TME and can get rid of the penetration limitation of traditional external light. Meanwhile, the dyad can generate chemiluminescence from S1, showing the potential of early cancer imaging owing to its inborn background-free characteristics. The outcomes of this project are expected to provide possibilities of early detection and intervention of cancer and reducing the obstacles of clinical transformation to improve patient survival.

癌症的早期诊断和治疗已引起广泛关注，但仍缺乏肿瘤成像和治疗相结合的技术。涉及功能性光敏染料的光动力疗法（PDT）被认为是一种潜在的解决方案。 PDT主要依靠光激活光敏剂（PS）来（1）通过发光视觉标记癌症和（2）产生过量的有毒活性氧（ROS）。然而，阻碍PDT应用的主要原因之一是激发光的组织穿透性有限。因此，解决深部PSs的激发问题并克服组织障碍对于高效的一体化癌症诊断和治疗具有重要意义。该项目将开发多功能集成自发光PDT平台，克服传统PDT光穿透有限的问题，实现原位肿瘤的同步诊断和治疗。 BODIPY-鲁米诺二元体将通过连接 BODIPY PS（具有长三重态寿命）与余辉鲁米诺来构建。在特定肿瘤微环境 (TME) 的触发下，二元体可以被化学能激活至单重激发态 (S1)，然后经历系间窜越至三重激发态，其中二元体使 O2 敏感，产生用于 PDT 的 1O2。 PDT过程依靠鲁米诺和TME之间的化学反应，可以摆脱传统外部光的穿透限制。同时，该二元体可以从S1产生化学发光，由于其固有的无背景特性，显示出早期癌症成像的潜力。该项目的成果预计将为癌症的早期发现和干预提供可能性，并减少临床转化的障碍，从而提高患者的生存率。