Controlling Nanoparticle Delivery in Hyperthermia for Cancer Treatment: Computational and in vivo Experimental Study

在许多工业化国家，癌症相关疾病是导致死亡的第二大原因。在现有的癌症治疗方法中，磁性纳米颗粒热疗，即磁性纳米颗粒在暴露于交变磁场时诱导肿瘤局部加热，由于其实施简单，高肿瘤细胞杀伤潜力，低成本和减少并发症而非常有前途。颗粒在肿瘤中的不适当沉积对肿瘤治疗产生不利的温度分布，特别是当肿瘤大小不规则时。纳米颗粒在生物组织和肿瘤中的分布以及这些纳米颗粒在各种治疗条件下诱导的加热模式尚不清楚。该提案解决了在给药过程中控制纳米颗粒在肿瘤细胞外空间分散的挑战，并制定了个性化的治疗策略，以实现最佳的治疗效果。主要研究方向为：(1)琼脂糖凝胶中的纳米流体传输；(2)在小鼠体内植入肿瘤，研究肿瘤血管对温度升高的影响；(3)基于不规则形状肿瘤多注射部位设计的磁热疗潜在场景传热模型。本研究提出的统一计算和体内实验方法有望促进对磁性纳米粒子热疗的基本认识，并使热控制算法和治疗方案的优化设计成为可能，从而提高肿瘤个体化治疗的疗效。拟议的研究将整合到研讨会系列和我们的课程中，以传播纳米生物科学和技术，以及在跨学科环境中教育和培训学生。该基金将为来自不同背景的学生提供充足的研究机会，参与体验式培训。

CONTROLLING NANOPARTICLE DELIVERY IN HYPERTHERMIA FOR CANCER TREATMENT: COMPUTATIONAL AND IN VIVO EXPERIMENTAL STUDY Ronghui Ma and Liang ZhuCancer-related illness is the second leading cause of death in many industrialized countries. Among available therapeutic methods in cancer treatment, magnetic nanoparticle hyperthermia, in which magnetic nanoparticles delivered to tumors induce localized heating when exposed to alternating magnetic fields, is highly promising due to its simple implementation, high tumor cell-killing potential, low cost, and reduced complications. Inappropriate deposition of the particles in tumor yields unfavorable temperature distribution for cancer therapy especially when the tumor has an irregular size. Distribution of nanoparticles in biological tissue and tumor and heating patterns induced by these nanoparticles under various therapeutic conditions are not well understood. The proposal addresses the challenge of control of the dispersion of nanoparticles in the extracellular space of tumor during the administration process and development of individualized therapeutic strategy to enable optimal treatment outcome. The research effort will focus on: (1) Nanofluid transport in agarose gel; (2) In vivo experiments performed on a tumor implanted in mice to investigate the effect of tumor vasculature on the temperature elevation; and (3) Heat transfer modeling of potential scenarios of magnetic hyperthermia to design strategy of multiple injection sites in irregularly shaped tumors. The unified computational and in vivo experimental approach proposed in the study is expected to advance fundamental understanding of magnetic nanoparticle hyperthermia and enables optimal design for a heat-control algorithm and treatment protocol with improved efficacy for individualized treatment of tumors. The proposed research will be integrated into seminar series and our curricula for disseminating nano-bioscience and technology as well as educating and training students in an interdisciplinary setting. The funding will provide students from diverse backgrounds with ample research opportunities to engage in experiential training.