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

SBIR 第 1 阶段 - 主题 394 - 利用放射局部激活或释放全身治疗的组合治疗方式。

• 批准号: 10019801
• 负责人: Xu Li
• 金额: $ 30万
• 依托单位: ZYMERON CORPORATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2020-06-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10019801
• 关键词: Biodistribution; Biological; Cherenkov Radiation; Drug Kinetics; Elements; Formulation; Heavy Metals; Human; Light; Mitochondria; Modality; PUVA Photochemotherapy; Patients; Phase; Photosensitization; Photosensitizing Agents; Planet Earth; Radiation; Radiation therapy; Radioisotopes; Reactive Oxygen Species; Roentgen Rays; Small Business Innovation Research Grant; System; Techniques; Therapeutic; Tissues; Transducers; base; biomaterial compatibility; clinical application; clinical translation; cytotoxic; luminescence; medication safety; nanoparticle; nanoparticle delivery; novel; targeted delivery; tumor

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.

光动力学疗法（Photodynamic therapy，PDT）是利用光束激活光敏剂产生细胞毒性活性氧（cytotoxic reactive oxygen species，ROS）的一种治疗方法，联合收割机与放射治疗（Radiation Therapy，RT）相结合是一种有效的治疗方法，特别是X射线局部激活光动力学疗法（X-ray beam to localize activate PDT，XPDT）。大多数关于XPDT的研究使用纳米闪烁体作为X射线换能器来激活光敏剂。然而，用于制备纳米闪烁剂的材料通常由稀土或重金属元素组成，这些元素具有显著的药物安全性问题，并且尚未研究它们在人体中的生物相容性和耐受性，因此限制了这种策略的临床转化。与基于纳米闪烁体的XPDT相比，X射线诱导的切伦科夫辐射提供了实现X-PDT的另一种方法。已经证明，当通过放射性核素或外部X射线束治疗时，生物组织（例如肿瘤）可以产生切伦科夫发光，并且技术进步使得切伦科夫辐射能够用于患者中的肿瘤跟踪的临床应用。有大量证据表明，光敏剂可以被高能X射线激活以产生ROS。在此基础上，Zymeron开发了一种多功能制剂，以实现基于X射线的RT和PDT的新型组合治疗模式。