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.