In Vivo Assessment of Localized Magnetic Fluid Hyperthermia for Ovarian Cancer

局部磁流体热疗治疗卵巢癌的体内评估

• 批准号: 8641997
• 负责人: Michelle Ann Barton
• 金额: $ 9.19万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-16 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8641997
• 关键词: Behavior; Biodistribution; Cancer Model; Clinic; Drug Kinetics; Elementary Particles; Ethylene Glycols; Frequencies; Goals; Hyperthermia; In Vitro; Induced Hyperthermia; Ligands; Liquid substance; Magnetism; Malignant Neoplasms; Malignant neoplasm of ovary; Molecular Weight; Movement; Ovarian; Peptides; Property; Radiolabeled; Reporter; Rotation; Safety; Spatial Behavior; Surface; Surface Properties; System; Temperature; Therapeutic; Toxic effect; Translations; University of Texas M D Anderson Cancer Center; anticancer research; base; cancer cell; cancer therapy; clinical application; design; ethylene glycol; fluorophore; in vivo; iron oxide; magnetic field; mouse model; nanoparticle; nanoscale; particle; radiotracer; research study; response; tool; tumor

ABSTRACT Hyperthermia induced by magnetic nanoparticles in high frequency alternating magnetic fields (AMF), or Magnetic Fluid Hyperthermia (MFH), is based on the delivery of thermal energy at the nano-scale to tumors using iron oxide based magnetic nanoparticles (MNP) and an externally applied AMF. This phenomenon is the result of particle rotation or movement of the magnetic dipole. The fact that energy is only dissipated under high-frequency and moderate amplitude fields that can be constrained to the tumor region make MFH a highly promising form of non-invasive, externally activated cancer treatment To this date, the prevailing paradigm in the field is that delivery of nanoscale particles to tumors can be achieved by passive targeting due to the enhanced permeation and retention (EPR) effect. However, in vivo experiments tumors suggest otherwise, thus, posing potential limitations on the successful translation of such systems to the clinic. The aforementioned discrepancy reveals a need to understand the in vivo spatial and temporal behavior of nanoparticles as a result of their surface physicochemical properties. To our knowledge, the relationship between surface properties and the resulting temporal and spatial behavior has not been investigated in orthotopic mouse models of cancer. T The long-term goal of this project is to develop MNPs as a clinically feasible tool by providing a comprehensive understanding from fundamental particle design to clinical application. The main objective of this proposal is to pursue the optimization ofthe spatial and temporal behavior of Magnetic Nanoparticle Heaters (MNH) and perform an in vivo efficacy assessment of targeted or

摘要 磁性纳米粒子在高频交变磁场(AMF)或磁流体热疗(MFH)中诱导的热疗是基于使用基于氧化铁的磁性纳米粒子(MNP)和外部应用的AMF将纳米级的热能传递到肿瘤上。这种现象是粒子旋转或磁偶极子运动的结果。事实上，能量仅在高频和中等幅度的磁场下耗散，这些磁场可以限制在肿瘤区域，使MFH成为一种非常有前途的非侵入性、外部激活的癌症治疗形式。到目前为止，该领域的主流范式是，由于增强的渗透和滞留(EPR)效应，可以通过被动靶向将纳米粒子输送到肿瘤。然而，活体肿瘤的实验表明并非如此，因此，对这种系统成功地转化到临床上构成了潜在的限制。上述差异揭示了由于纳米粒子的表面物理化学性质而需要了解其在体内的空间和时间行为的必要性。据我们所知，在原位癌症小鼠模型中，表面特性和由此产生的时间和空间行为之间的关系还没有被研究过。T 该项目的长期目标是通过提供从基本粒子设计到临床应用的全面了解，将MNPs开发为临床可行的工具。这项建议的主要目标是追求磁性纳米加热器(MNH)的空间和时间行为的优化，并执行体内靶向或