Transport of magnetic nanoparticles through soft tissue using gradient fields

描述（由申请人提供）：目前正在开发生物相容性磁性微米/纳米颗粒作为靶向药物和基因递送剂、磁共振成像造影剂和热消融机制。然而，由于在精确地控制颗粒在体内的运动和在目标部位充分地集中颗粒的能力方面的限制，磁性颗粒用于医学应用的潜力尚未完全实现。对于许多应用，磁性颗粒必须在所施加的场的影响下迁移通过软组织以到达期望的位置。需要更好地了解影响磁性纳米颗粒（MNP）通过软组织运动的因素，以充分利用这些颗粒的潜力。因此，该项目的目的是表征磁性纳米颗粒通过软组织的运动。我们的假设是，MNP通过软组织的运动取决于MNP的大小和形状，所施加的磁场的特性和粒子移动通过的组织的特性。在研究这一假设，我们提出了以下具体目标：目的1：制定和表征家庭的超顺磁性纳米粒子的可变特性。目的2：研究MNP特性和变化磁场对MNP在粘性液体和凝胶中流动性的影响。目标3：研究基质（包括纯凝胶和含3D包埋细胞培养物的凝胶组成的软组织模型）的粘弹性对MNP迁移率的影响。临床相关性：在拟议的研究中获得的数据将显着有助于我们了解磁介导的颗粒通过软组织的运输。这些信息将为进一步开发MNP的治疗和诊断应用提供基础，包括靶向治疗，热消融和MRI造影剂。

DESCRIPTION (provided by applicant): Biocompatible magnetic micro/nanoparticles are currently being developed as targeted drug and gene delivery agents, magnetic resonance imaging contrast agents and as thermoablation mechanisms. However, the potential of magnetic particles for medical applications has not been fully realized due to limitations in the capability to accurately control the movement of the particles in vivo and to adequately concentrate the particles at the target site. For many applications the magnetic particles must migrate through soft tissue under the influence of an applied field to reach the desired location. A better understanding of the factors that influence the movement of magnetic nanoparticles (MNP) through soft tissue is required to fully exploit the potential of these particles. The purpose of this project, therefore, is to characterize the movement of magnetic nano-particles through soft tissues. Our hypothesis is that the movement of MNPs through soft tissues is dependent on the size and shape of the MNPs, the characteristics of the applied magnetic field and the properties of the tissues through which the particles move. In investigate this hypothesis we propose the following specific aims: Aim 1: To formulate and characterize a family of superparamagnetic nanoparticles with variable characteristics. Aim 2: Investigate the effects of MNP characteristics and varying magnetic fields on MNP mobility in viscous liquid and gel. Aim 3: Investigate the effects of visco-elastic properties of matrices (including soft tissue models composed of pure gels and gels with 3D embedded cell cultures) on MNP mobility. Clinical relevance: The data obtained in the proposed studies will significantly contribute to our understanding of the magnetically mediated transport of particles through soft tissues. This information will provide the basis for further development of therapeutic and diagnostic applications of MNPs including targeted therapies, thermal ablation, and MRI contrast agents.