Transport of magnetic nanoparticles through soft tissue using gradient fields

描述(由申请人提供)：生物相容的磁性微米/纳米颗粒目前正在被开发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，由于在精确控制粒子在体内的运动和在靶点充分浓缩粒子的能力方面的限制，磁性粒子在医疗应用中的潜力还没有完全实现。对于许多应用，磁性颗粒必须在外加磁场的影响下通过软组织移动才能到达所需位置。为了充分利用磁性纳米颗粒的潜力，需要更好地了解影响磁性纳米颗粒(MNP)在软组织中移动的因素。因此，这个项目的目的是描述磁性纳米粒子在软组织中的运动。我们的假设是，MNPs在软组织中的移动取决于MNPs的大小和形状、外加磁场的特性以及粒子通过的组织的性质。在研究这一假说时，我们提出了以下具体目标：目标1：设计和表征一类具有不同特性的超顺磁性纳米粒子。目的：研究MNP特性和不同磁场对MNP在粘性液体和凝胶中迁移率的影响。目的：研究基质材料(包括由纯凝胶和三维细胞培养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极大地有助于我们理解磁性颗粒通过软组织的传输。这些信息将为进一步开发MNPs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.