A Systematic Correlation of Nanoparticle Size with Diffusivity through Biological Fluids

Nanomedicine, the application of nanotechnology for medical purposes, has been widely identified as a potential solution for today‟s healthcare problems. Nanomedicine uses the "bottom-up‟ principles of nanoscale engineering to improve areas of medicine which have previously been considered undevelopable. One of the enduring challenges for medicine is the design of innovative devices able to overcome biological barriers, allowing drugs and therapeutics to effectively reach their correct location of action. Biological barriers are a defence mechanism of the body which are extremely well-evolved to protect the body from foreign and harmful particles. Therapeutic drugs and devices, which are not harmful, are often identified by the body as dangerous because their composition differs from native and accepted entities. The traversal of these biological barriers, such as mucus, remains a bottleneck in the progress of drug delivery and gene therapy. The mucus barrier physically limits the motion of particles due to its complicated mesh structure which obstructs the particles' traversal path. Mucus fibres can also adhere to the particles, entrapping them and restricting their motion. Particle traversal of mucus is carried out by passive diffusion. As diffusion has traditionally been defined by the Stokes-Einstein equation as inversely proportional to particle radius, it follows that reducing particle sizes into the nanoscale would result in increased diffusive ability. These predictions, however, do not consider the obstructive effects of the complicated mesh structure for the case of mucus. The exact effect of reducing particle size into the nanoscale for diffusion through mucus is therefore unknown. Multiple Particle Tracking was used to obtain real-time movies of the diffusion of nanoparticles, ranging from 12nm – 220nm in diameter, through mucus samples. The experimental data generated was used to systematically correlate the relationship between particle size and diffusivity through mucus. This study reveals that nanoparticles, smaller than the average pore size in the mucus mesh structure, can diffuse through lower viscosity pores which pose less resistance to diffusive motion, allowing nanoparticles to travel at up to four times the speed expected from the bulk viscosity of the mucus. This type of information can help researchers understand the importance of size for therapeutic nanoparticles, allowing researchers to decide whether attempts to decrease nanoparticle size at the expense of other functionality are worthwhile

High Rydberg State Carbon Recombination Lines from Interstellar Clouds

We report observations of carbon recombination lines near 34.5 MHz (qunatum number n=578) and 325 MHz (n=272) made towards Cas A, the Galactic centre and about ten other directions in the galactic plane. Constraints on the physical conditions in the line forming regions are derived from these and other existing observations. The CII regions that produce the low-frequency lines are most likely associated with the neutral HI component of the ISM.Comment: 4 pages, 3 figures; Presented at the workshop on "New Perspects on the Interstellare Medium", Penticton, Canada, Aug 199

Correlations in the multispecies PASEP on a ring

Ayyer and Linusson studied correlations in the multispecies TASEP on a ring (Trans AMS, 2017) using a combinatorial analysis of the multiline queues construction defined by Ferrari and Martin (AOP, 2008). It is natural to explore whether an analogous application of appropriate multiline queues could give similar results for the partially asymmetric case. In this paper, we solve this problem of correlations of adjacent particles on the first two sites in the multispecies PASEP on a finite ring. We use the multiline processes defined by Martin (EJP, 2020), the dynamics of which also depend on the asymmetry parameter $q$, to compute the correlations

Chemotherapeutic Applications of Rhodamine Based NanoGUMBOS

The work presented in this dissertation employs nanomaterials derived from a group of uniform materials based on organic salts (GUMBOS) for selective chemotherapeutic applications. GUMBOS, similar to ionic liquids, are organic salts consisting of a bulky cationic and anionic moiety. In contrast to ionic liquids, these materials have melting points ranging from 25–250 °C, making them solid phase at room temperature. Similar to ionic liquids, GUMBOS display tunable properties, such as hydrophobicity and solubility, through counter ion variation. These tunable properties provide a variety of applications for these GUMBOS, including selective chemotherapeutics applications. The work in this dissertation evaluates the chemotherapeutic behavior of a series of nanomaterials, i.e, nanoGUMBOS, derived from rhodamine dyes to examine the role of both anion variation as well as cation structure on the therapeutic efficacy of the nanoparticle. Firstly, the mechanism of selective toxicity of previously investigated rhodamine 6G (R6G) nanoGUMBOS was determined. Interestingly, these R6G nanoGUMBOS displayed internalization via endocytosis in cancer cells while they lacked endocytic internalization in normal cells. This variation in internalization pathways ultimately resulted in the observed selective behavior of these R6G nanoGUMBOS. In my second project, the role of cyclodextrin (CD) templating on the size and selective chemotherapeutic behavior of these R6G nanoGUMBOS was evaluated. These CD-templated nanoGUMBOS displayed a remarkable two to three-fold increase in toxicity with no effect on selectivity. In my latter two chapters, the therapeutic efficacy of nanoGUMBOS derived from various rhodamine dyes is examined to assess the role of cation structure on selective chemotherapeutic behavior. Intriguingly, a significant difference was found in the selective behavior of GUMBOS derived from ester and carboxylic acid derivatives. In this regard, nanoGUMBOS derived from ester derivatives displayed selective chemotherapeutics toxicity similar to that of R6G nanoGUMBOS. In contrast, GUMBOS derived from carboxylic acid rhodamines displayed non-selective behavior, suggesting that the selectivity was structure dependent. Further examination of a triple nanoGUMBOS structure corroborated these results as modification of the carboxylic acid structure led to complete selectivity of these nanoGUMBOS under examined conditions. Moreover, these studies demonstrate the promising therapeutic potential and advantages of rhodamine based nanoGUMBOS for selective chemotherapeutic applications