SBIR Phase 1 - Topic 394 - Combinatory Treatment Modalities Utilizing Radiation to Locally Activate or Release Systemically Delivered Therapeutics.

光动力疗法(PDT)利用光束激活光敏剂产生细胞毒性活性氧(ROS)，与放射治疗(RT)相结合是一种有效的治疗方法，特别是利用X射线局部激活光动力学疗法(XPDT)。大多数关于XPDT的研究都使用纳米闪烁体作为X射线换能器来激活光敏剂。然而，用于制备纳米闪烁体的材料通常由稀土或重金属元素组成，这些元素具有重大的药物安全性问题，并且它们在人体内的生物相容性和耐受性尚未得到研究，从而限制了此类策略的临床翻译。与基于纳米闪烁体的XPDT相比，X射线诱导的切伦科夫辐射为实现X-PDT提供了一种替代途径。已有研究表明，肿瘤等生物组织经放射性核素或外X射线照射后均可产生切伦科夫发光，技术的进步使切伦科夫辐射在临床上应用于肿瘤示踪成为可能。有大量证据表明，光敏剂可以被高能X射线激活而产生ROS。在此基础上，Zymeron开发了一种多功能配方，以实现基于X射线的RT和PDT的新型组合治疗模式。

Photodynamic therapy (PDT) utilizes light beam to activate photosensitizers to produce cytotoxic reactive oxygen species (ROS), and it has been proposed as a potent treatment to combine with Radiation Therapy (RT), especially for the idea of using X-ray beam to locally activate PDT (XPDT). Majority studies about XPDT have used nanoscintillators as the X-ray transducer to activate photosensitizers. However, the materials used to prepare nanoscintillators usually consist of rare-earth or heavy metal elements which possess a significant drug safety issue and their biocompatibility and tolerability in humans have not been studied, thus limiting the clinical translation of such strategies. Compared to the nanoscintillator-based XPDT, Cherenkov radiation induced by X-ray provides an alternative approach to realize X-PDT. It has been demonstrated that biological tissues such as tumors can produce Cherenkov luminescence when treated by either radionuclides or external X-ray beams and the technique advances have enabled the clinical application of Cherenkov radiation for tumor tracking in patients. There are numerous evidences that photosensitizers can be activated by high energy X-ray to generate ROS. Based on this, Zymeron develops a multi-functional formulation to allow a novel combinational treatment modality of X-ray-based RT and PDT.