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引起了广泛的关注，但是，仍然缺乏整合肿瘤成像和治疗剂的技术。涉及功能性光敏染料的光动力疗法（PDT）被认为是潜在的解决方案。 PDT主要依赖于光激活的光敏剂（PSS）用于（1）具有发光的视觉标记癌症，（2）产生过量的有毒活性活性氧（ROS）。但是，阻碍PDT应用的主要原因之一是激发光的组织渗透有限。因此，解决深层部位中PS的激发问题并克服组织障碍对于有效的多一体癌症诊断和治疗具有重要意义。该项目将开发一个多功能集成的自我释放的PDT平台，该平台可以克服常规PDT中有限的光穿透性，从而可以同步诊断和对原位肿瘤的治疗。 Bodipy-Luminol Dyads将通过将Bodipy PSS（长三重寿命）与余辉卢米尔醇连接起来来构建。在由特定肿瘤微环境（TME）触发的触发后，可以通过化学能量到单线激发态（S1）激活二元组，然后在gointersystems Crossing到三重态激发态，其中二元组将O2敏化以产生1O2的PDT。 PDT过程取决于Luminol和TME之间的化学反应，并可以摆脱传统外部光线的渗透限制。同时，二元组可以从S1产生化学发光，显示出由于其天生的无背景特征而产生的早期癌症成像的潜力。预计该项目的结果将提供癌症早期检测和干预的可能性，并减少临床转化的障碍，以提高患者生存。