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

高强度聚焦超声（HIFU）消融近来已获得认可用于治疗有限的癌症类型，例如，局限性前列腺癌HIFU手术不是常规进行的，因为与局部癌症的标准治疗相比，其靶向有效性仍然不确定。将金纳米粒子直接注射到皮下肿瘤中的HIFU消融显示出由于独特的声热现象而增强的消融，同时减少了邻近正常组织中的热损伤。然而，直接注射金纳米粒子的HIFU消融尚未充分发挥其潜力，因为它主要治疗浅表肿瘤，并且注射部位的异质金纳米粒子浓度导致不均匀的加热曲线。我们的目标是实现目标的聚焦消融在降低HIFU功率水平使用功能化的金纳米粒子增强能量沉积。使用HIFU加热全身注射的金纳米粒子来消融深层癌症可以指导未来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，加强了与美国FDA的持续合作，从而使医疗和工业界受益。与以往一样，将积极招募本科生/少数民族学生。长期目标是开发选择性靶向和消融深部肿瘤的HIFU-金-纳米粒子消融方法。假设暴露于降低的HIFU功率的全身注射的功能化金纳米颗粒将导致肿瘤靶向的改善，并实现均匀的热沉积，同时最大限度地减少对周围组织的附带损伤。为了检验这一假设，将使用动物模型来评估注射到循环中的功能化金纳米颗粒与降低的HIFU功率组合将实现前列腺癌的精确靶向和均匀消融的功效。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表达的特定细胞表面标记。预计全身注射的功能化金纳米颗粒将选择性地靶向深层癌症;并且它们可用于成像和消融前列腺癌组织，对相邻组织的附带损伤最小。这项初步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，从而开发出一种治疗癌症组织的新型消融方法。该奖项反映了NSF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.