High-intensity focused ultrasound (HIFU) energized functionalized nanoparticles mediated enhanced thermal ablation of tumors

近年来，高强度聚焦超声（HIFU）消融术已获得认可，可用于治疗有限类型的癌症，例如局限性前列腺癌。HIFU手术没有常规进行，因为与局部癌症的标准治疗相比，其靶向效果仍不确定。由于独特的声热现象，直接向皮下肿瘤注射金纳米颗粒的HIFU消融显示出增强的消融，同时减少了邻近正常组织的热损伤。然而，直接注射金纳米颗粒的HIFU消融尚未充分发挥其潜力，因为它主要治疗浅表肿瘤，而且注射部位的金纳米颗粒浓度不均匀导致加热曲线不均匀。目的是利用功能化金纳米颗粒增强能量沉积，在降低HIFU功率水平下实现聚焦消融。使用HIFU加热全身注射的金纳米颗粒来消融深部癌症，可以指导未来更大规模的动物研究和人类治疗计划。这项独特的跨学科研究将癌症治疗、纳米材料、生物传热、波传播、图像分析和非侵入性手术方法等领域联系起来，扩大了与美国FDA的持续合作，从而使医学界和工业界受益。一如既往地积极招收本科生和少数民族学生。长期目标是开发hifu -金纳米颗粒消融方法，选择性地靶向和消融深部肿瘤。据推测，系统注射的功能化金纳米颗粒暴露在较低的HIFU功率下，将提高肿瘤的靶向性，实现均匀的热沉积，同时最大限度地减少对周围组织的附带损伤。为了验证这一假设，将使用动物模型来评估将功能化金纳米颗粒注射到循环系统中并结合降低HIFU功率的效果，以实现前列腺癌的精确靶向和均匀消融。纳米技术将用于开发功能性金纳米颗粒，可以识别前列腺癌细胞上过度表达的特定细胞表面标记物。系统注射功能化金纳米颗粒有望选择性靶向深部肿瘤；它们可以用来成像和切除前列腺癌组织对邻近组织的附带损害最小。这项试点研究有望提供原理证明，即癌症组织可以吸收多功能金纳米颗粒，并可以选择性消融，从而开发一种新的消融方法来治疗癌症组织。这种协议将改善癌症患者的护理和疾病管理。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

High-intensity focused ultrasound (HIFU) ablation has gained endorsement in recent times for treating limited cancer types, e.g., localized prostate cancer. HIFU procedure is not routinely conducted because its targeting effectiveness remained uncertain when compared to standard treatments for localized cancers. HIFU ablation in presence of direct injection of gold nanoparticles into subcutaneous tumors have shown enhanced ablation due to unique acoustic-thermal phenomenon, while thermal damage in adjacent normal tissues was reduced. However, HIFU ablation with direct gold-nanoparticles injection has yet to achieve its full potential because it primarily treats superficial tumors and that the heterogeneous gold-nanoparticles concentration at the injection site leads to uneven heating profiles. The objective is to achieve the goal of focused ablation at reduced HIFU power levels using functionalized-gold-nanoparticles enhanced energy deposition. The use of HIFU heating of systemically injected gold-nanoparticles for ablating deep-seated cancer could guide future larger-scale animal studies and treatment planning in humans. This unique interdisciplinary study links fields of cancer therapy, nanomaterials, bio-heat transfer, wave propagation, image analysis, and non-invasive surgical method, augmenting ongoing collaborations with US FDA and, in turn, benefiting medical and industry community. Undergraduate/minority students will be actively recruited as in the past.The long-term goal is to develop HIFU-gold-nanoparticles ablation methods that selectively target and ablate deep-seated tumors. It is hypothesized that systemically injected functionalized-gold-nanoparticles exposed to reduced HIFU power will lead to improved targeting of tumors and enable uniform heat deposition, while minimizing collateral damage to surrounding tissues. To test the hypothesis, animal models with will be used to assess the efficacy by which functionalized gold-nanoparticles injected into the circulation combined with reduced HIFU power will achieve precise targeting and uniform ablation of prostate cancer. Nanotechnology will be used to develop functional gold-nanoparticles that can recognize specific cell-surface markers overexpressed on prostate cancer cells. It is expected that systemically injected functionalized-gold-nanoparticles will selectively target deep-seated cancer; and that they can be used to both image and ablate prostate cancer tissues with minimal collateral damage to adjacent tissues. This pilot research is expected to provide proof-of-principle that cancer tissues can take up multifunctional gold-nanoparticles and can be selectively ablated, thus developing a novel ablation approaches to treat cancer tissues. Such protocol would improve cancer patient care and management of disease.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.