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

癌症的早期诊断和治疗已经引起了人们的广泛关注，然而，目前还缺乏将肿瘤影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。光动力疗法主要依赖于光激活光敏剂(PSS)来实现：(1)用发光来直观地标记癌症；(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对组织的穿透性有限。因此，解决PSS在深层部位的激发问题，克服组织障碍，对于有效的肿瘤一体化诊断和治疗具有重要意义。该项目将开发一种多功能集成自发光PDT平台，该平台可以克服传统PDT中有限的光穿透，使原位肿瘤的同步诊断和治疗成为可能。通过将BODIPY PSS(具有长三重态寿命)与余辉鲁米诺连接起来，可以构建BODIPY-鲁米诺二元系。在特定的肿瘤微环境(TME)的触发下，二联体可被化学能激活为单重态激发态(S1)，然后在系间交叉进入三重态激发态，在此过程中二联体敏化O2以产生光动力(PDT)。光动力学过程依赖于鲁米诺和TME之间的化学反应，可以摆脱传统外部光的穿透限制。同时，二聚体可以从S1产生化学发光，由于其与生俱来的无背景特性，显示了早期癌症成像的潜力。该项目的成果有望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，以提高患者的存活率。

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.