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.

光动力疗法（PDT）利用光束激活光敏剂来产生细胞毒性活性氧（ROS），并已提议作为一种有效的治疗方法与放射疗法（RT）结合，尤其是用于使用X射线束以局部激活PDT（XPDT）的想法。关于XPDT的多数研究已使用纳米阶级示波器作为X射线传感器来激活光敏剂。但是，用于制备纳米激素的材料通常由具有重大药物安全问题的稀土或重金属元素组成，并且尚未研究其在人类中的生物相容性和耐受性，因此限制了此类策略的临床翻译。与基于纳米激素的XPDT相比，由X射线诱导的Cherenkov辐射提供了一种实现X-PDT的替代方法。已经证明，当通过放射性核素或外部X射线束治疗时，肿瘤等生物组织可以产生Cherenkov发光，并且该技术的进步使Cherenkov辐射在患者的肿瘤跟踪中的临床应用。有许多证据表明，高能X射线可以激活光敏剂以生成ROS。基于此，Zymeron开发了一种多功能配方，以允许基于X射线的RT和PDT的新型组合处理方式。