S. (Srinivas) Sridhar
Latika Menon, Donald E. Heiman
Date of Award
Doctor of Philosophy
Department or Academic Unit
College of Arts and Sciences. Department of Physics.
physics, nanoscience, assembly, drug release, magnetic targeting, MRI contrast, nanoplatforms, nanotemplates
Nanoplatforms are nanoscale structures designed as general platforms for multi-functional nanotechnology applications. Applications of nanotechnology cover broad spectrum of research fields and require true interdisciplinary and multidisciplinary studies. It also requires a fundamental understanding of physical principles in nanoscale since nanomaterials exhibit different properties and experience distinct forces compared to the materials in macroscale. In this thesis, we studied two different nanoplatforms, namely nanoporous oxide coatings and superparamagnetic nanoparticles. We analyzed their physical properties and illustrated their applications in two different fields, nanomanufacturing and nanomedicine.
The first nanoplatform we studied is ordered nanoporous arrays of aluminum and titanium oxide. We investigated their fabrication as well as their applications in both nanomanufacturing and nanomedicine. We addressed the question of assembling spherical and cylindrical elements into porous holes - all in the same nanoscale. To investigate the assembly of nanoelements, one has to have an understanding of forces in nanoscale. In this length scale, the electronic and magnetic forces are the dominant forces whereas some macroscale forces like gravity has none to little effect. We demonstrated 3D directed assembly of nanobeads as well as single-wall carbon nanotubes (SWNT) into nanoholes by means of electrophoresis and dielectrophoresis at ambient temperatures. For nanobead assembly, SEM images were sufficient to demonstrate 100% assembly of loaded nanobeads. For SWNT , the connection through assembled nanotubes were used to prove the success of the assembly. The I-V measurements clearly showed that strong Si-SWNT interconnects carrying currents on the order of 1 mA were established inside the nanoholes. This assembly technique is particularly useful for large-scale, rapid, 3D assembly of 106 SWNT over a centimeter square area under mild conditions for nanoscale semiconductor electronics applications.
We also demonstrated that nanoporous oxide coatings can be utilized as non-eroding sustained drug release platforms for up to weeks of elution. The release kinetics was explained in two main regions: burst and sustained release. The sustained release kinetics for nanoporous coatings was characterized as an activated surface density dependent desorption model in form of df/dt = -α f exp(-β f2 / kB T). Nanoporous inorganic coatings were proved to be well suited to provide improved efficacy and integration of implants in a variety of therapeutic situations like drug eluting stents or antibiotic coated hip replacements.
The second type of nanoplatform we investigated is magnetic nanoparticles. Magnetic properties differ in nanoscale due to the increasing role of the surface spins as the particle size is decreased, leading very interesting phenomenon like superparamagnetism. We studied magnetic properties of nanoparticles, namely superparamagnetic iron oxide nanoparticles (SPION). Magnetic properties of SPION was studied through superconducting quantum interference device (SQUID) magnetization as well as nuclear magnetic resonance (NMR) spectroscopy measurements. We showed that SPION can be successfully encapsulated inside micelle and liposome structures to create versatile theranostic nanoplatforms for enhanced drug delivery and monitoring of cancer treatment. The ability to incorporate SPION cargo renders these nanoplatforms to be highly susceptible to guidance by external magnetic fields, as well as making them exceptional magnetic resonance imaging (MRI) contrast agents, enabling visualization of their distribution in vivo.
The efficacy of using magnetic immuno-micelles (MIM) and magnetic cationic liposomes (MCL) for magnetic targeting and as MRI contrast agents was investigated using in vitro NMR and in-vivo MRI studies. For micelle study, human breast carcinoma cells were incubated with specific anti-body attached MIM. NMR measurements showed not only MIM affect T2 relaxation time of the sample, but also the cell binding of MIM was higher with specific (2C5) anti-body compared to non-specific anti-body or control groups.
For liposome study, metastatic melanoma tumor was grown in the right flank of SCID mice. Magnetic targeting was employed by placing a disk magnet on top of the tumor of the animal after administration of MCL for one hour. Pre-injection and post-injection MR images were used to assess response to magnetic targeting effects. Hypointense areas in MR images, decreased signal intensity, and lower T2* relaxation times all directly correlated to MCL accumulation. We showed that with the help of magnetic targeting the accumulation and retention of MCL was 2-fold higher in the tumor side compared to control groups.
Gultepe, Evin, "Physics of nanoplatforms and their applications in nanomanufacturing and nanomedicine" (2009). Physics Dissertations. Paper 16. http://hdl.handle.net/2047/d20000058
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