Exploring controlled drug release from magneto-liposomes by alternating and pulsed magnetic fields

智力价值：该提案的目的是探索通过使用超顺磁性Fe/Fe3O4纳米棒的机械旋转来控制单层脂肪体外膜的破坏，纳米棒将充当纳米搅拌棒。纳米粒子的机械旋转将同时受到连续和脉冲磁场的驱动。其假设是，纳米搅拌棒的磁场诱导运动会破坏脂质体的单层双层结构，从而在不显著升高温度的情况下导致亲水性负载的快速释放。这一方法将允许将热敏感药物(如抗癌药物)输送到其生物靶标。本研究的目的是提高对磁性纳米颗粒机械运动如何触发生物相关过程的基本理解，以便优化药物输送的磁脂质体。该方案提出了产生强磁场和脉冲磁场的实验计划。连续交变磁场处理的脂质体的原位动态光散射将被用来监测脂质体的尺寸和相稳定性。原位法拉第旋转和时间分辨荧光实验将有助于获得核心区和膜区内粘度的动态信息，以及超分子脂质双层/磁性纳米粒子组装在短脉冲磁场下的溶解-重建。拟议的机械触发脂质体给药将能够将几乎任何药物输送到身体的任何位置。更广泛的影响：该项目的结果可能会导致一种新的物理方法，通过磁场产生受控释放药物。此外，该项目还将提供磁性纳米颗粒的机械运动如何影响膜流动性的定量数据。堪萨斯州立大学化学系将创建一个为期一周的街区课程，以提高他们的学生？生物物理化学和纳米医学的前景：PI和Co-PI将开发和教授一门名为？纳米粒子作为癌症治疗中的有效载荷和释放的触发器？在春季学期，作为材料化学课程的一部分。本课程将向所有兽医、化学、生物化学、生物和物理专业的研究生和本科生开放。这项研究将有助于将这项研究扩展到堪萨斯州立大学正在进行的磁热疗合作努力中。这项研究还将为REU(本科生的研究经验)、SUROP(暑期本科生研究机会计划)和DSP(发展中的学者？)创造机会。计划)学生在堪萨斯州立大学。拟议的脉冲磁场系统的仪器开发将在美国中西部创建一个独特的设施，该设施将向与其他大学和研究机构的合作开放。

Intellectual Merit: The aim of the proposal is to explore controlled disruption of the outer membranes of unilamellar lipsomes by using the mechanical rotation of superparamagnetic Fe/Fe3O4 nanorods, which will act as nano stir bars. The mechanical rotation of the nanoparticles will be driven by both continuous and pulsed magnetic fields. The hypothesis is that the unilamellar bilayers of the liposomes will be disrupted by the magnetic field induced motion of the nano stir bars, resulting in the quick release of the hydrophilic payload without a significant increase in temperature. This approach will permit the delivery of thermosensitive drugs (e.g. anticancer drugs) to their biological targets.The objective of this proposed research is to improve the basic understanding of how mechanical movement of magnetic nanoparticles can trigger biologically relevant processes in order to optimize magneto-liposomes for pharmaceutical delivery. Experimental plans to generate strong and pulsed magnetic fields are presented in this proposal. In situ dynamic light scattering of liposomes treated with continuous alternating magnetic fields will be used to monitor the size and phase stability of the liposomes. In situ Faraday rotation and time-resolved fluorescence experiments will help obtain dynamical information of the inner viscosities of core- and membrane-regions, as well as dissolution-reconstruction of supramolecular lipid bilayer/magnetic nanoparticle assemblies upon exposure to short pulsed magnetic fields. The proposed drug delivery by mechanically triggered liposomes will be able to deliver virtually any drug to any position of the body. Broader Impact: The results from the project could potentially lead to a new physical method to produce controlled release of drugs by magnetic fields. In addition, the project will provide quantitative data how the membrane fluidity is affected by the mechanical motion of magnetic nanoparticles. The Department of Chemistry at Kansas State University will create one block course for the duration of one week in order to enhance their students? perspective on biophysical chemistry and nanomedicine: The PI and Co-PI will develop and teach a block course entitled ?Nanoparticles as Payloads and Triggers for Release in Cancer Therapy? during the spring semester as a part of the ?Material Chemistry Course?. This course will be open to all graduate and undergraduate students in veterinary medicine, chemistry, biochemistry, biology and physics. The research will help extend this research to ongoing collaborative efforts on magnetic hyperthermia at Kansas State University. The research will also create opportunities to incoming REU (Research Experience of Undergraduates), SUROP (Summer Undergraduate Research Opportunity Program) and DSP (Developing Scholars? Program) students at Kansas State University. The proposed instrumental development of a pulsed magnetic field system will create a unique facility in the Midwestern United States, which will be open to collaborations with other universities and research institutions.