Optimization of Heating Pattern in Magnetic Nanoparticle Hyperthermia: Compuational and in vivo Experimental Study

磁性纳米颗粒热疗加热模式的优化：计算和体内实验研究

• 批准号: 0828728
• 负责人: Ronghui Ma
• 金额: $ 29.08万
• 依托单位: University of Maryland Baltimore County
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0828728&HistoricalAwards=false
• 关键词: Optimization; Heating; Pattern; Magnetic; Nanoparticle

CBET-0828728MaAmong available therapeutic methods in cancer treatment, magnetic nanoparticle hyperthermia emerges as a highly promising approach due to its simple implementation, low cost, and few complications. In this process, magnetic particles delivered to tissue or blood vessels induce heating when exposed to alternating magnetic fields. This localized heat generation leads to thermal damage to the tumor. The employment of nano-sized particles enables adequate amount of heat to be generated within tumor tissue without necessitating heat penetration through the skin surface, thus eliminating the consequent side effects of excessive collateral thermal damage. Although the versatility of magnetic nanoparticle hyperthermia in treating deep-seated/irregular shaped tumors is unsurpassed by traditional non-invasive heating approaches, this method is severely limited by the lack of controlling the temperature elevations during the process. The non-homogeneous temperature distribution and inadequate temperature elevation in tumor tissue may lead to inadequacy in killing tumor cells and/or damage to healthy tissue. Multiple-site injection of nanoparticles has great potential for achieving a desired temperature elevation throughout the entire tumor region, but requires optimized injection strategy including injection sites, injection amount, and injection rate. Therefore, in the proposed study an in vivo experimental study of magnetic nanoparticle hyperthermia on tumors implanted on mice and a multi-scale computational study of nanoparticle transport in biological tissue will be performed with the aims of advancing understanding of nanofluid transport in tumor and quantifying the heating patterns induced by these nanoparticles under various therapeutic conditions. The ultimate outcome of this project is the development of a global methodology for designing individualized treatment protocol for irregular shaped tumors. Intellectual Merit: The findings of this study will (1) significantly advance understanding of nanoparticle transport in tissue and magnetic nanoparticle-induced heating pattern in hyperthermia treatment of cancer; (2) provide a platform on which the effect of particle properties, tissue microstructures, and injection strategy on the migration of particles and heating patterns in tumors can be tested; (3) establish a database describing the dependence of thermally affected region on injection parameters; and (4) develop of an optimized treatment strategy using multi-site injection. The capability of quantifying the induced heating pattern by nanoparticles in tumors is an important advance that moves the treatment planning from an almost empirical trial-and-error approach to a science-based engineering methodology. Broader Impact: The proposed study will be integrated into our seminar series and curricula for disseminating bio-nanotechnology as well as educating and training students in an interdisciplinary setting. Both PIs have established track records of commitment for promoting underrepresented minority students in STEM fields. The funding will provide our students from diverse backgrounds with ample research opportunities to engage in experiential training. Transformative essence: This study will lead to a global methodology for designing an optimized, patient-specific treatment protocol for magnetic nanoparticle hyperthermia with maximum treatment outcomes in clinical applications. The success of magnetic nanoparticle hyperthermia will offer cancer patients a low cost treatment method that has high tumor cell-killing potential and minimal complications. In addition, the study of nanoparticle migration in tissue will benefit the study of nanotoxicology and site-specific drug delivery using nanomaterials. This project is jointly funded by the Thermal Transport Processes (TTP) Program, the Biomedical Engineering (BME) Program, and the Fluid Dynamics (FD) Program, all of the Chemical, Bioengineering, Environmental, and Transport Systems (CBET) Division within the Directorate for Engineering (ENG).

在癌症治疗的可用治疗方法中，磁性纳米颗粒热疗由于其简单的实施、低成本和很少的并发症而成为非常有前途的方法。在这个过程中，当暴露于交变磁场时，递送到组织或血管的磁性颗粒会引起加热。这种局部热产生导致肿瘤的热损伤。纳米尺寸的颗粒的使用使得能够在肿瘤组织内产生足够量的热量，而不需要通过皮肤表面的热渗透，从而消除过度附带热损伤的后续副作用。虽然磁性纳米粒子热疗在治疗深部/不规则形状肿瘤中的多功能性是传统的非侵入性加热方法所无法超越的，但这种方法受到缺乏控制过程中温度升高的严重限制。肿瘤组织中的非均匀温度分布和不充分的温度升高可能导致杀死肿瘤细胞的不充分和/或对健康组织的损伤。纳米颗粒的多部位注射具有在整个肿瘤区域实现所需温度升高的巨大潜力，但需要优化的注射策略，包括注射部位、注射量和注射速率。因此，在拟议的研究中，将进行磁性纳米颗粒热疗对小鼠植入肿瘤的体内实验研究和生物组织中纳米颗粒运输的多尺度计算研究，目的是促进对肿瘤中纳米流体运输的理解，并量化这些纳米颗粒在各种治疗条件下诱导的加热模式。该项目的最终成果是开发一种全球方法，用于设计不规则形状肿瘤的个性化治疗方案。智力优势：本研究的发现将（1）显著推进对纳米粒子在组织中的运输和磁性纳米粒子在癌症热疗中诱导的加热模式的理解;（2）提供一个平台，在该平台上可以测试粒子性质、组织微观结构和注射策略对粒子在肿瘤中的迁移和加热模式的影响;（3）建立描述热影响区对注射参数依赖性的数据库;（4）开发使用多部位注射的优化治疗策略。通过肿瘤中的纳米颗粒量化诱导加热模式的能力是一个重要的进步，它将治疗计划从几乎经验性的试错方法转变为基于科学的工程方法。更广泛的影响：拟议的研究将被纳入我们的研讨会系列和课程，以传播生物纳米技术，以及教育和培训学生在跨学科的设置。这两个PI都建立了在STEM领域促进代表性不足的少数民族学生的承诺记录。这笔资金将为来自不同背景的学生提供充足的研究机会，以进行体验式培训。变革本质：这项研究将导致一个全球性的方法，用于设计一个优化的，患者特定的治疗方案，用于磁性纳米粒子热疗，在临床应用中具有最大的治疗效果。磁性纳米粒子热疗的成功将为癌症患者提供一种低成本的治疗方法，具有高肿瘤细胞杀伤潜力和最小的并发症。此外，纳米粒子在组织中迁移的研究将有利于纳米毒理学和纳米材料的定点给药研究。该项目由热传输过程（TTP）计划，生物医学工程（BME）计划和流体动力学（FD）计划共同资助，所有这些都是工程局（ENG）内的化学，生物工程，环境和运输系统（CBET）部门。