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The Effect of Nanoparticle Diameter on TAT-mediated Delivery to the CNS In Vivo

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Neurological disorders are difficult to treat with current drug delivery methods due to their inefficiency and the lack of knowledge of the mechanisms behind drug delivery across the blood brain barrier (BBB). Nanoparticles (NPs) are a promising drug delivery method

Neurological disorders are difficult to treat with current drug delivery methods due to their inefficiency and the lack of knowledge of the mechanisms behind drug delivery across the blood brain barrier (BBB). Nanoparticles (NPs) are a promising drug delivery method due to their biocompatibility and ability to be modified by cell penetrating peptides, such as transactivating transciptor (TAT) peptide, which has been shown to increase efficiency of delivery. There are multiple proposed mechanisms of TAT-mediated delivery that also have size restrictions on the molecules that can undergo each BBB crossing mechanism. The effect of nanoparticle size on TAT-mediated delivery in vivo is an important aspect to research in order to better understand the delivery mechanisms and to create more efficient NPs. NPs called FluoSpheres are used because they come in defined diameters unlike polymeric NPs that have a broad distribution of diameters. Both modified and unmodified 100nm and 200nm NPs were able to bypass the BBB and were seen in the brain, spinal cord, liver, and spleen using confocal microscopy and a biodistribution study. Statistically significant differences in delivery rate of the different sized NPs or between TAT-modified and unmodified NPs were not found. Therefore in future work a larger range of diameter size will be evaluated. Also the unmodified NPs will be conjugated with scrambled peptide to ensure that both unmodified and TAT-modified NPs are prepared in identical fashion to better understand the role of size on TAT targeting. Although all the NPs were able to bypass the BBB, future work will hopefully provide a better representation of how NP size effects the rate of TAT-mediated delivery to the CNS.

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2016-05

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Plasmonic nanoparticles and their suspensions for solar energy conversion

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Plasmon resonance in nanoscale metallic structures has shown its ability to concentrate electromagnetic energy into sub-wavelength volumes. Metal nanostructures exhibit a high extinction coefficient in the visible and near infrared spectrum due to their large absorption and scattering cross sections

Plasmon resonance in nanoscale metallic structures has shown its ability to concentrate electromagnetic energy into sub-wavelength volumes. Metal nanostructures exhibit a high extinction coefficient in the visible and near infrared spectrum due to their large absorption and scattering cross sections corresponding to their surface plasmon resonance. Hence, they can serve as an attractive candidate for solar energy conversion. Recent papers have showed that dielectric core/metallic shell nanoparticles yielded a plasmon resonance wavelength tunable from visible to infrared by changing the ratio of core radius to the total radius. Therefore it is interesting to develop a dispersion of core-shell multifunctional nanoparticles capable of dynamically changing their volume ratio and thus their spectral radiative properties. Nanoparticle suspensions (nanofluids) are known to offer a variety of benefits for thermal transport and energy conversion. Nanofluids have been proven to increase the efficiency of the photo-thermal energy conversion process in direct solar absorption collectors (DAC). Combining these two cutting-edge technologies enables the use of core-shell nanoparticles to control the spectral and radiative properties of plasmonic nanofluids in order to efficiently harvest and convert solar energy. Plasmonic nanofluids that have strong energy concentrating capacity and spectral selectivity can be used in many high-temperature energy systems where radiative heat transport is essential. In this thesis,the surface plasmon resonance effect and the wavelength tuning ranges for different metallic shell nanoparticles are investigated, the solar-weighted efficiencies of corresponding core-shell nanoparticle suspensions are explored, and a quantitative study of core-shell nanoparticle suspensions in a DAC system is provided. Using core-shell nanoparticle dispersions, it is possible to create efficient spectral solar absorption fluids and design materials for applications which require variable spectral absorption or scattering.

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Date Created
2012

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Nano- and micro-scale temperature measurements using laser-induced fluorescence thermometry

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A method of determining nanoparticle temperature through fluorescence intensity levels is described. Intracellular processes are often tracked through the use of fluorescence tagging, and ideal temperatures for many of these processes are unknown. Through the use of fluorescence-based thermometry, cellular

A method of determining nanoparticle temperature through fluorescence intensity levels is described. Intracellular processes are often tracked through the use of fluorescence tagging, and ideal temperatures for many of these processes are unknown. Through the use of fluorescence-based thermometry, cellular processes such as intracellular enzyme movement can be studied and their respective temperatures established simultaneously. Polystyrene and silica nanoparticles are synthesized with a variety of temperature-sensitive dyes such as BODIPY, rose Bengal, Rhodamine dyes 6G, 700, and 800, and Nile Blue A and Nile Red. Photographs are taken with a QImaging QM1 Questar EXi Retiga camera while particles are heated from 25 to 70 C and excited at 532 nm with a Coherent DPSS-532 laser. Photographs are converted to intensity images in MATLAB and analyzed for fluorescence intensity, and plots are generated in MATLAB to describe each dye's intensity vs temperature. Regression curves are created to describe change in fluorescence intensity over temperature. Dyes are compared as nanoparticle core material is varied. Large particles are also created to match the camera's optical resolution capabilities, and it is established that intensity values increase proportionally with nanoparticle size. Nile Red yielded the closest-fit model, with R2 values greater than 0.99 for a second-order polynomial fit. By contrast, Rhodamine 6G only yielded an R2 value of 0.88 for a third-order polynomial fit, making it the least reliable dye for temperature measurements using the polynomial model. Of particular interest in this work is Nile Blue A, whose fluorescence-temperature curve yielded a much different shape from the other dyes. It is recommended that future work describe a broader range of dyes and nanoparticle sizes, and use multiple excitation wavelengths to better quantify each dye's quantum efficiency. Further research into the effects of nanoparticle size on fluorescence intensity levels should be considered as the particles used here greatly exceed 2 ìm. In addition, Nile Blue A should be further investigated as to why its fluorescence-temperature curve did not take on a characteristic shape for a temperature-sensitive dye in these experiments.

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Date Created
2011

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Molecular Dynamic Simulations of Diffusion and Phase Behaviors of Colloidal Particles in Two-Component Liquid Systems

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A comprehensive and systematic investigation on the diffusion and phase behaviors of nanoparticles and macromolecules in two component liquid-liquid systems via Molecule Dynamic (MD) simulations is presented in this dissertation.

The interface of biphasic liquid systems has attracted great attention because

A comprehensive and systematic investigation on the diffusion and phase behaviors of nanoparticles and macromolecules in two component liquid-liquid systems via Molecule Dynamic (MD) simulations is presented in this dissertation.

The interface of biphasic liquid systems has attracted great attention because it offers a simple, flexible, and highly reproducible template for the assembly of a variety of nanoscale objects. However, certain important fundamental issues at the interface have not been fully explored, especially when the size of the object is comparable with the liquid molecules. In the first MD simulation system, the diffusion and self-assembly of nanoparticles with different size, shape and surface composition were studied in an oil/water system. It has been found that a highly symmetrical nanoparticle with uniform surface (e.g. buckyball) can lead to a better-defined solvation shell which makes the “effective radius” of the nanoparticle larger than its own radius, and thus, lead to slower transport (diffusion) of the nanoparticles across the oil-water interface. Poly(N-isopropylacrylamide) (PNIPAM) is a thermoresponsive polymer with a Lower Critical Solution Temperature (LCST) of 32°C in pure water. It is one of the most widely studied stimulus-responsive polymers which can be fabricated into various forms of smart materials. However, current understanding about the diffusive and phase behaviors of PNIPAM in ionic liquids/water system is very limited. Therefore, two biphasic water-ionic liquids (ILs) systems were created to investigate the interfacial behavior of PNIPAM in such unique liquid-liquid interface. It was found the phase preference of PNIPAM below/above its LCST is dependent on the nature of ionic liquids. This potentially allows us to manipulate the interfacial behavior of macromolecules by tuning the properties of ionic liquids and minimizing the need for expensive polymer functionalization. In addition, to seek a more comprehensive understanding of the effects of ionic liquids on the phase behavior of PNIPAM, PNIPAM was studied in two miscible ionic liquids/water systems. The thermodynamic origin causes the reduction of LCST of PNIPAM in imidazolium based ionic liquids/water system was found. Energy analysis, hydrogen boding calculation and detailed structural quantification were presented in this study to support the conclusions.

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Date Created
2017