Multifunctional and tunable lipid-nanoparticle assemblies

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Multifunctional nano scale therapeutics represents a transformative new frontier in disease treatment. Liposomes provide a versatile and dynamic platform for encapsulating functional inorganic nanoparticles with different surface chemistries to achieve multiple therapeutic objectives. This project employs original approaches to selectively decorate engineered liposomes with inorganic nanoparticles, and examine how nanoparticle size, charge and hydrophobicity affect liposome structure and function. Such composite assemblies will play an important role in therapeutic applications where spatially as well as temporally targeted delivery is required. Surface functionalized superparamagnetic iron oxide (SPIO) will be used as model nanoparticles, as they have been successfully employed as MRI contrast agents and for in vivo hyperthermia, where heating is achieved using external magnetic fields operating at radio frequencies. Programmed RF stimulation of the magnetoliposomes will provide a simple yet robust way to control liposome structure and stability. Through Aim 1, electrostatically and hydrophobically assembled decorated magnetoliposomes will be formed and their structure, morphology, and colloidal stability characterized. In Aim 2, the effect of selective decoration, SPIO nanoparticle lipid interactions, and RF-heating on lipid phase behavior will be studied. In Aim 3, selective transbilayer permeability of a molecule encapsulated within the magnetoliposomes will be demonstrated via controlled-release or a novel burst-release mechanism through programmed RF heating.Intellectual Merit. The ability to selectively control phase behavior, heat, and mass transfer in soft colloidal nanoscale systems is highly desirable for the formation of next generation multifunctional therapies, nanoparticles, nanomaterials, and nanodevices. Localized RF heating in bilayers is an original concept that is expected to provide selective control over bilayer phase behavior, and in turn diffusion. This project will provide new experimental methods for the synthesis and characterization of hybrid nanoparticle/lipid assemblies. Hence, the integration of inorganic nanoparticles and biomolecular systems will be extended to include this unique class of active nanomaterials. Characterizing thermodynamic and transport properties will provide a complete picture of the assemblies, which will be needed to determine their potential as multifunctional therapeutic agents. For instance, the decorated magnetoliposomes may enhance drug delivery by providing an external trigger and yielding time and dose dependent diffusion. By inverting the problem, we also have identified a way to use the magnetoliposomes as a potential nanoscale temperature sensor.Broader Impacts. Given the minimally invasive nature and tissue penetration of RF-heating, these novel carriers would be very effective for manipulating the delivery of therapeutic agents in vivo. Opportunities are being pursued with faculty from the College of Pharmacy at URI to identify promising applications. In addition, these new structures provide suitable model systems for studying nanoparticle interactions with cellular membranes, including their role in uptake and potential toxicity. This project will also serve as an educational tool for high school, undergraduate, and graduate students. Co-PI Bose organizes a summer high school intern program and both PIs have been contacted by and will work with the New England LSAMP program to mentor students. Within our diverse laboratory groups, we intend to pair high school and undergraduate students with graduate student mentors to conduct independent projects directly related to hybrid liposomes. This activity will expand the impact of the project to beyond the traditional and expected research participation. The concepts behind this project and the results obtained will be used as teaching material in a new interdisciplinary graduate level Bionanotechnology course offered in the spring semester, and disseminated freely through a collaborative website.