Enhancing High-Intensity Focused Ultrasound for Tumor Ablation with Phase-Changing Nanoagents

使用相变纳米制剂增强高强度聚焦超声用于肿瘤消融

• 批准号: 9278962
• 负责人: Ange Gloria Nyankima
• 金额: $ 3.72万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-16 至 2019-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9278962
• 关键词: Ablation; Acoustics; Area; Asia; Award; Back; Behavior; Blood Circulation; Burn injury; Caliber; Cardiovascular system; Cell Death; Characteristics; Clinical; Communities; Contrast Media; Data; Deposition; Development; Diagnostic Imaging; Disease; Dose; Effectiveness; Encapsulated; Europe; Excision; Extravasation; Fluorocarbons; Focused Ultrasound Therapy; Formulation; Future; Gases; Generations; Goals; Half-Life; Heating; Hour; Image; Injury; Knowledge; Lead; Lesion; Liquid substance; Location; Mechanics; Mediating; Medical; Metastatic Neoplasm to the Bone; Methods; Microbubbles; Microscopy; Modeling; Multiple Tumor Masses; Mus; Nature; Necrosis; Operative Surgical Procedures; Optics; Outcome; Pathology; Penetration; Performance; Permeability; Physiologic pulse; Pilot Projects; Process; Property; Recovery; Research Proposals; Rodent; Safety; Site; Skin; Specificity; Surgical complication; Techniques; Technology; Temperature; Testing; Therapeutic Uses; Thermal Ablation Therapy; Thinness; Time; Tissues; Translations; Treatment Efficacy; Ultrasonic Therapy; Ultrasonic wave; Ultrasonography; Uterine Fibroids; Work; base; cancer diagnosis; clinical application; clinical translation; clinically significant; design; effective therapy; imaging modality; improved; in vivo; melanoma; nanoDroplet; nanometer; nanoparticle; nanosized; new technology; novel; particle; phase change; pre-clinical; prevent; public health relevance; tool; tumor; tumor ablation

 DESCRIPTION (provided by applicant): The demand for safe and effective therapeutic technology continues to increase as worldwide cancer diagnoses increase. High intensity focused ultrasound (HIFU) is a promising option to focus acoustic energy for non-surgical ablation of tumors, while avoiding surgical complications and long recovery times. With HIFU, acoustic energy is delivered to a target location, and in the process, causes warranted damage by over-heating the tissue and/or causing mechanical injury. There remain concerns with HIFU regarding long surgical time, high energy requirements, and off-target effects, such as skin burns, due to acoustic energy delivery requirements. A new technology which could increase the amount of heating delivered to the site of pathology, while reducing off-target thermal damage would be highly clinically significant. Microbubbles have shown potential to decrease energy requirements by providing enhanced conversion of acoustic energy to thermal and mechanical energy through cavitation. Limitations in microbubble diameter prevent extravasation outside the circulatory system, and their thin shells give them a very short half-lif in vivo. Phase-changing nanoagents (PCNAs), a novel nanoparticle in the field of ultrasound, can be developed by compressing the gas-core of microbubbles into a liquid. These agents possess a diameter range of several hundred nanometers, likely capable of extravasating through the leaky vasculature of tumors and accumulating in tumors due to the enhanced permeability and retention (EPR) effect. In the following proposal we aim to optimize nanoagent formulation and improve HIFU performance through further development of PCNAs. Little has been done in regards to evaluating and optimizing in vivo PCNA behavior, specifically optimizing their extravasation and accumulation potential as well as evaluating their circulation time in vivo. We propose to work towards generation of a PCNA designed to accumulate in tumors and provide sustained tumor circulation, which can be used for HIFU ablation effectively. PCNA properties will be modified by varying the type of perfluorocarbon gas used, the diameter distribution of PCNA formulation, and the shell composition. Ideal nanoagents for HIFU will have properties of long circulation time, long accumulation time inside tumors with little deposition in healthy tissue, and enhanced ablation at the target with minimal off-target damage. PCNA formulations will be tested in the treatment of mouse melanoma tumors to test this hypothesis. It is the hope that the successful completion of all three proposed aims will demonstrate the versatility of the nanoagents and advance the PCNA technology for clinical applications in ultrasound for therapy and diagnostic imaging.

 描述（由申请人提供）：随着全球癌症诊断的增加，对安全有效的治疗技术的需求持续增加。高强度聚焦超声 (HIFU) 是聚焦声能以非手术消融肿瘤的一种有前途的选择，同时避免手术并发症和较长的恢复时间。通过 HIFU，声能被传递到目标位置，并在此过程中通过使组织过热和/或造成机械损伤而造成必要的损坏。由于声能输送要求，HIFU 仍然存在手术时间长、能量要求高以及脱靶效应（例如皮肤烧伤）等问题。一项新技术可以增加传递到病理部位的热量，同时减少脱靶热损伤，这将具有高度的临床意义。微泡已显示出通过空化增强声能向热能和机械能的转化，从而降低能量需求的潜力。微泡直径的限制可以防止其外渗到循环系统之外，而且它们的薄壳使它们在体内的半衰期非常短。相变纳米制剂（PCNA）是超声波领域的一种新型纳米颗粒，可以通过将微泡的气核压缩成液体来开发。这些药物的直径范围为数百纳米，可能能够通过肿瘤的渗漏脉管系统外渗，并由于增强的渗透性和保留（EPR）效应而在肿瘤中积聚。在以下提案中，我们的目标是通过进一步开发 PCNA 来优化纳米制剂配方并提高 HIFU 性能。在评估和优化体内 PCNA 行为，特别是优化其外渗和积累潜力以及评估其体内循环时间方面，几乎没有开展任何工作。我们建议致力于生成一种 PCNA，旨在在肿瘤中积累并提供持续的肿瘤循环，可有效用于 HIFU 消融。 PCNA 特性将通过改变所用全氟化碳气体的类型、PCNA 配方的直径分布和壳成分来改变。理想的 HIFU 纳米药物应具有循环时间长、在肿瘤内积聚时间长、肿瘤内沉积少的特点。 健康组织，增强目标消融，同时将脱靶损伤降至最低。 PCNA 制剂将在小鼠黑色素瘤的治疗中进行测试，以验证这一假设。希望所有三个拟议目标的成功完成将展示纳米制剂的多功能性，并推动 PCNA 技术在超声治疗和诊断成像的临床应用。