Investigation of nanobubble nucleation by radiation therapy

放射治疗纳米气泡成核的研究

• 批准号: 10642367
• 负责人: Guillem Pratx
• 金额: $ 19.33万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642367
• 关键词: 3-Dimensional; Acoustics; Alpha Particles; Basic Science; Biological; Biological Assay; Biophysical Process; Cancer Patient; Caring; Cells; Clinical; Combined Modality Therapy; Cosmic Radiation; Darkness; Diagnostic; Dose; Dose Limiting; Exposure to; Focused Ultrasound; Focused Ultrasound Therapy; Gases; Hour; Human; In Vitro; Incidence; Investigation; Ionizing radiation; Kinetics; Lead; Liquid substance; Malignant Neoplasms; Measurement; Measures; Mechanics; Medicine; Membrane; Modality; Modeling; Neutrons; Normal tissue morphology; Optical Methods; Organ; Organelles; Organism; Outcome; Patients; Predisposition; Property; Radiation; Radiation Dose Unit; Radiation therapy; Reactive Oxygen Species; Resistance; Risk; Sampling; Scanning; Scheme; Seminal; Temperature; Therapeutic; Tissues; Toxic effect; Translations; Treatment Efficacy; Tumor Volume; Ultrasonics; Ultrasonography; Water; cell killing; clinical practice; design; experimental study; improved; in vivo; in vivo Model; innovation; ionization; irradiation; microscopic imaging; millimeter; nanobubble; nanosized; neoplastic cell; novel; particle; physical property; prevent; radioresistant; response; treatment planning; treatment strategy; tumor; ultrasound

Abstract This project investigates a little-known physical property of ionizing radiation, which has the potential to increase the therapeutic ratio of radiation therapy (RT). Several decades ago, it was observed that ionizing radiation could nucleate gas nanobubbles (NBs) in water and other liquids. Seminal experiments revealed the presence of NB in irradiated water, which manifested as a decrease in the ultrasound power required to achieve acoustic cavitation. These results raise a crucial yet unanswered question: Does ionizing radiation nucleate NBs in vivo, inside irradiated tissues? Radiation is widely used in medicine. The premise that NBs may be nucleated in patients during diagnostic scans or radiation therapy is significant because NBs could induce biological effects. In addition, their presence in the tissues may lower the threshold for acoustic cavitation, which suggest a novel mechanism for increasing the efficacy of radiation therapy. The first Aim of this project is to gather rigorous and comprehensive evidence of NB nucleation in irradiated cells in vitro. Sensitive assays, including darkfield microscopy and ultrasound imaging, will be used to detect NBs in cells after exposure to ionizing radiation. This study will generate quantitative estimates of the efficiency of NB nucleation for different types of radiation, including their kinetics and stability under different conditions. The second Aim is to explore the use of radiation- induced NB to enhance the therapeutic efficacy of RT. Given that exogenously administered NBs are already used to increase the efficacy of high-intensity focused ultrasound (HIFU), intrinsically induced NBs nucleated during exposure to ionizing radiation should have similar enhancing effect for HIFU. Therapeutic efficacy of this combined treatment will be assessed by treating multicellular tumor spheroids sequentially with RT and HIFU, then quantitatively assessing the biological response of the cells. The proposed combination uses treatment modalities approved for use in humans and requires no extrinsic agents to be administered. This combination of radiation-induced NB nucleation and ultrasound-driven NB cavitation is a highly innovative and practical solution to the issue of treatment-resistant tumors.

抽象的 该项目调查了电离辐射的鲜为人知的物理特性，这有可能增加 放射治疗（RT）的治疗比率。几十年前，观察到电离辐射可以 水和其他液体中的核气纳米泡（NB）。开创性实验揭示了NB的存在 在辐照的水中，这表现为实现声学所需的超声功率的降低 空化。这些结果提出了一个至关重要但未解决的问题：电离辐射在体内是否有核NBS？ 内部辐照组织？辐射广泛用于医学。 NB可以在 在诊断扫描或放射治疗期间患者很重要，因为NBS可以诱导生物学作用。 此外，它们在组织中的存在可能会降低声气膜的阈值，这表明了一种新颖的 提高放射治疗功效的机制。该项目的第一个目的是收集严格的和 在体外辐照细胞中NB成核的综合证据。敏感测定法，包括Darkfield 暴露于电离辐射后，显微镜和超声成像将用于检测细胞中的NB。这 研究将产生NB成核效率的定量估计值，以不同类型的辐射， 包括它们在不同条件下的动力学和稳定性。第二个目的是探索辐射的使用 - 诱导的NB增强了RT的治疗功效。鉴于外源给药的NB已经是 用于提高高强度聚焦超声（HIFU）的疗效，本质上诱导的NBS成核 在暴露于电离辐射期间，HIFU应具有相似的增强作用。治疗功效 联合治疗将通过用RT和HIFU依次处理多细胞肿瘤球体来评估。 然后定量评估细胞的生物学反应。提出的组合使用治疗 批准用于人类的模式，不需要施用外在药物。这种组合 辐射引起的NB成核和超声驱动的NB空化是一种高度创新且实用的解决方案 到耐药性肿瘤的问题。